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Embryotoxic and Teratogenic Effects of Norfloxacin in Pregnant Female Albino Rats
This study was designed to investigate the possible developmental teratogenicity of norfloxacin in rats. Forty pregnant female rats were divided into four equal groups. Group A received norfloxacin in a dose of 500?mg/kg·b·wt/day orally from 6th to 15th day of gestation. Groups B and C received 1000 and 2000?mg/kg·b·wt/day orally for the same period, respectively; Group D behaved as control and received 0.5?mL distilled water orally for the same period. The dams were killed on 20th day of gestation and their fetuses were subjected to morphological, visceral, and skeletal examinations. Norfloxacin significantly decreased the number of viable fetuses, increased the number of resorbed fetuses, and induced retardation in growth of viable fetuses; some visceral and skeletal defects in these fetuses were seen and these effects were dose dependant. Conclusively, norfloxacin caused some fetal defects and abnormalities, so it is advisable to avoid using this drug during pregnancy.
Elbadawy, Mohamed; Soliman, Ahmed; El-Hewaity, Mohamed
The effect of ethylmercury on fetal development and some essential metals levels in fetuses and pregnant female rats
Ethylmercuric chloride (EtHg), at the dose of 2.5 mg Hg\\/kg, was administered by gavage every other day to pregnant rats from\\u000a d 6 to 20 of gestation. On the 21st day of gestation, females were sacrificed to allow the evaluation of embryotoxicity and\\u000a take the material for analytical determinations. Copper, zinc, iron, and calcium were determined by AAS in liver,
J. Chmielnicka; E. Brze?nicka; B. BARAIqSKI; K. Sitarek
Cadmium causes delayed effects on renal function in the offspring of cadmium-contaminated pregnant female rats.
In the adult rat, chronic cadmium intoxication induces nephropathy with Fanconi-like features. This result raises the question of whether intoxication of pregnant rats has any deleterious effects on renal function in their offspring. To test this hypothesis, we measured the renal function of 2- to 60-day-old postnatal offspring from female rats administered cadmium chloride by the oral route (0.5 mg.kg(-1).day(-1)) throughout their entire gestation. Investigations of rat offspring from contaminated pregnant rats showed the presence of cadmium in the kidney at gestational day 20. After birth, the cadmium kidney concentration increased from postnatal day 2 to day 60 (PND2 to PND60), presumably because of 1) milk contamination and 2) neonatal liver cadmium content release. Although the renal parameters (glomerular filtration, U/P inulin, and urinary excretion rate) were not significantly affected until PND45, renal failure appeared at PND60, as demonstrated by a dramatic decrease of the glomerular filtration rate associated with increased excretion of the main ions. In parallel, an immunofluorescence study of tight-junction protein expression of PND60 offspring from contaminated rats showed a disorganization of the tight-junction proteins claudin-2 and claudin-5, specifically expressed in the proximal tubule and glomerulus, respectively. In contrast, expression of a distal claudin protein, claudin-3, was not affected. In conclusion, in utero exposure of cadmium leads to toxic renal effects in adult offspring. These results suggest that contamination of pregnant rats is a serious and critical hazard for renal function of their offspring. PMID:17686954
Jacquillet, G; Barbier, O; Rubera, I; Tauc, M; Borderie, A; Namorado, M C; Martin, D; Sierra, G; Reyes, J L; Poujeol, P; Cougnon, M
Vitamin A supplementation to pregnant and breastfeeding female rats induces oxidative stress in the neonatal lung.
Vitamin A is an essential micronutrient that regulates many biological processes through modulation of retinoic acid receptor-responsive genes. Vitamin A acts as a systemic antioxidant, participating in the modulation of diverse redox mechanisms involved in physiological and pathological processes. Different studies, however, observed that vitamin A and other retinoids may induce pro-oxidant/deleterious actions under certain conditions, leading to impairment of brain and lung function. Here, we studied the effect of vitamin A treatment at oral doses of 100 IU/kg, 200 IU/kg, and 300 IU/kg to female rats (Rattus norvegicus) during pregnancy and lactation on oxidative parameters of lungs from the offspring vitamin A supplementation induced increases in lipoperoxidation, protein carbonyl, activities of the antioxidant enzymes superoxide dismutase and catalase (200 IU/kg, and 300 IU/kg), and decreased sulphydryl protein (500 IU/kg) content in the neonatal lung. PMID:20679000
Pasquali, Matheus Augusto de Bittencourt; Schnorr, Carlos Eduardo; Feistauer, Lucas Brambilla Hilbig; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca
The Vanished Pregnant Body in Psychoanalytic Female Developmental Theory
The author contends that the pregnant body—the premier icon of the mature female body—has vanished from our psychoanalytic theory of female development. Until we are able to restore this missing entity on a par with the phallus, the developmental theory for both sexes remains fixated in phallocentricism. The author traces some of the evidence for this claim in a brief
Rosemary H. Balsam
Effects of exposure to microwaves on cellular immunity and placental steroids in pregnant rats.
OBJECTIVES: Microwaves produce various detrimental changes based on actions of heat or non-specific stress, although the effects of microwaves on pregnant organisms has not been uniform. This study was designed to clarify the effect of exposure to microwaves during pregnancy on endocrine and immune functions. METHODS: Natural killer cell activity and natural killer cell subsets in the spleen were measured, as well as some endocrine indicators in blood--corticosterone and adrenocorticotrophic hormone (ACTH) as indices of the hypothalamic-pituitary-adrenal axis--beta-endorphin, oestradiol, and progesterone in six female virgin rats and six pregnant rats (nine to 11 days gestation) exposed to microwaves at 10 mW/cm2 incident power density at 2450 MHz for 90 minutes. The same measurements were performed in control rats (six virgin and six pregnant rats). RESULTS: Skin temperature in virgin and pregnant rats increased immediately after exposure to microwaves. Although splenic activity of natural killer cells and any of the subset populations identified by the monoclonal antibodies CD16 and CD57 did not differ in virgin rats with or without exposure to microwaves, pregnant rats exposed to microwaves showed a significant reduction of splenic activity of natural killer cells and CD16+CD57-. Although corticosterone and ACTH increased, and oestradiol decreased in exposed virgin and pregnant rats, microwaves produced significant increases in beta-endorphin and progesterone only in pregnant rats. CONCLUSIONS: Microwaves at the power of 10 mW/cm2 produced activation of the hypothalamic-pituitary-adrenal axis and increased oestradiol in both virgin and pregnant rats, suggesting that microwaves greatly stress pregnant organisms. These findings in pregnant rats suggest that--with exposure to microwaves--pregnancy induces immunosuppression, which could result in successful maintainance of pregnancy. This enhancement of adaptability to heat stress with pregnancy may be mediated by activation of placental progesterone and placental or pituitary beta-endorphin.
Nakamura, H; Seto, T; Nagase, H; Yoshida, M; Dan, S; Ogino, K
Association between obesity and periodontitis in pregnant females.
Background: The purpose of this study is to investigate whether overweight and obesity before pregnancy are associated with periodontitis during pregnancy. Methods: This study examined a total of 315 pregnant females at 21 to 24 weeks of gestation. Overweight and obesity were defined based on criteria proposed by the World Health Organization Expert Consultation. Periodontal conditions were assessed by measuring clinical periodontal attachment loss (AL). To investigate whether obese pregnant females have increased risk according to the extent of periodontitis, the data were divided into two groups: 1) generalized periodontitis and 2) localized periodontitis. A comparison among underweight, normal-weight, and overweight/obese groups for explanatory variables was analyzed using the ?(2) test for categorical variables and an analysis of variance for continuous variables. Multivariate logistic regression analysis was performed with adjustments for age, health and oral health behaviors, and obstetric information. Results: Age, age at first delivery, periodontitis, and periodontal conditions (two or more interproximal sites with AL ?4 mm not on the same tooth) were significantly associated with body mass index (BMI) (P <0.05). The adjusted odds ratio of periodontitis was 4.57 (95% confidence interval = 2.30 to 9.07) for overweight and obese females (BMI ?23 kg/m(2)), after adjusting for all of the covariates. Conclusion: There is a strong association between prepregnancy overweight/obesity and periodontitis in pregnant females. PMID:24502613
Lee, Hyo-Jin; Jun, Jong-Kwan; Lee, Seung-Mi; Ha, Jung-Eun; Paik, Dai-Il; Bae, Kwang-Hak
Uteroplacental insufficiency programmes vascular dysfunction in non-pregnant rats: compensatory adaptations in pregnancy
Intrauterine growth restriction is a risk factor for cardiovascular disease in adulthood. We have previously shown that intrauterine growth restriction caused by uteroplacental insufficiency programmes uterine vascular dysfunction and increased arterial stiffness in adult female rat offspring. The aim of this study was to investigate vascular adaptations in growth restricted female offspring when they in turn become pregnant. Uteroplacental insufficiency was induced in WKY rats by bilateral uterine vessel ligation (Restricted) or sham surgery (Control) on day 18 of pregnancy. F0 pregnant females delivered naturally at term. F1 Control and Restricted offspring were mated at 4 months of age and studied on day 20 of pregnancy. Age-matched non-pregnant F1 Control and Restricted females were also studied. Wire and pressure myography were used to test endothelial and smooth muscle function, and passive mechanical wall properties, respectively, in uterine, mesenteric, renal and femoral arteries of all four groups. Collagen and elastin fibres were quantified using polarized light microscopy and qRT-PCR. F1 Restricted females were born 10–15% lighter than Controls (P < 0.05). Non-pregnant Restricted females had increased uterine and renal artery stiffness compared with Controls (P < 0.05), but this difference was abolished at day 20 of pregnancy. Vascular smooth muscle and endothelial function were preserved in all arteries of non-pregnant and pregnant Restricted rats. Collagen and elastin content were unaltered in uterine arteries of Restricted females. Growth restricted females develop compensatory vascular changes during late pregnancy, such that region-specific vascular deficits observed in the non-pregnant state did not persist in late pregnancy.
Mazzuca, Marc Q; Tare, Marianne; Parkington, Helena C; Dragomir, Nicoleta M; Parry, Laura J; Wlodek, Mary E
Effects of local anesthetics on contractions of pregnant and non-pregnant rat myometrium in vitro.
In order to determine whether local anesthetics directly affect the propagation and strength of myometrial contractions, we compared the effects of bupivacaine, ropivacaine, lidocaine and tetracaine on the contractions of myometrium isolated from pregnant and non-pregnant rats. Full-thickness myometrial strips were obtained from 18- to 21-day pregnant and non-pregnant Sprague-Dawley rats and incubated in an organ bath. When spontaneous contractions became regular, strips were exposed to cumulative concentrations of the four local anesthetics ranging from 0.01 to 300 ?mol/L and the amplitude and frequency of contraction were recorded. All four compounds caused a concentration-dependent inhibition of the contractility of pregnant and non-pregnant uterine muscle. In pregnant myometrium, the concentration that caused 50% inhibition (IC50) was 100 ?mol/L for bupivacaine, 157 ?mol/L for ropivacaine, > 1000 ?mol/L for lidocaine, and 26.3 ?mol/L for tetracaine. In non-pregnant myometrium, the IC50 was 26.9 ?mol/L for bupivacaine, 40 ?mol/L for ropivacaine, 384 ?mol/L for lidocaine, and 7.4 ?mol/L for tetracaine. These results suggested that local anesthetics do inhibit myometrial contractions in pregnant and non-pregnant rats in a concentration-dependent manner. PMID:24901082
Wei, Jin-Song; Jin, Zhe-Bin; Yin, Zhi-Qiang; Xie, Qiang-Min; Chen, Ji-Qiang; Li, Zi-Gang; Tang, Hui-Fang
Megaloblastic hematopoiesis in a 20 year old pregnant female
Summary Background: Nitrous oxide can cause disordered blood cell proliferation and lead to pancytopenia and altered immune function. Case Report: A young pregnant female patient presented after binge nitrous oxide abuse with altered mental status and abnormal vital signs. From her initial assessment she was noted to have pancytopenia and was found to have megaloblastic, hyper-cellular changes in a subsequent bone marrow biopsy. This presentation was determined to be secondary to toxic effects after heavy use of nitrous oxide. Conclusions: Nitrous oxide exposure, including use as an inhalant, over 12 hours can lead to bone marrow abnormalities such as megaloblastic hematopoiesis.
Trivette, Evan T.; Hoedebecke, Kyle; Berry-Caban, Cristobal S.; Jacobs, Brandy R.
Increase in conversion of tryptophan to niacin in pregnant rats.
There is the report that the deaths by pellagra in women is approximately twofold excess that in men. In the present experiment, in order to clarify a factor in the etiology of pellagra in female and to get basic information how much niacin should be supplemented in pregnant state, we investigated the effects of pregnant on the metabolism of tryptophan to niacin in rats. The daily urine samples were collected from day -17 and day +6 (the delivery day was designated as day 0) and the intermediates of tryptophan to niacin were measured. The metabolites such as kynurenic acid, xanthurenic acid, anthranilic acid, 3-hydroxyanthranilic acid, quinolinic acid, N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, N1-methyl-4-pyridone-3-carboxamide were increased with progress in pregnant and returned to normal levels after the delivery. The catabolism of tryptophan is accelerated during pregnancy, indicataing that pregnancy would not be an etiology of pellagra and no niacin supplement needs but tryptohan supplement would need. PMID:15206761
Shibata, Katsumi; Fukuwatari, Tsutomu; Murakami, Mayumi; Sasaki, Ryuzo
Luteal activity of pregnant rats with hypo-and hyperthyroidism
Background Luteal activity is dependent on the interaction of various growth factors, cytokines and hormones, including the thyroid hormones, being that hypo- and hyperthyroidism alter the gestational period and are also a cause of miscarriage and stillbirth. Because of that, we evaluated the proliferation, apoptosis and expression of angiogenic factors and COX-2 in the corpus luteum of hypo- and hyperthyroid pregnant rats. Methods Seventy-two adult female rats were equally distributed into three groups: hypothyroid, hyperthyroid and control. Hypo- and hyperthyroidism were induced by the daily administration of propylthiouracil and L-thyroxine, respectively. The administration began five days before becoming pregnant and the animals were sacrificed at days 10, 14, and 19 of gestation. We performed an immunohistochemical analysis to evaluate the expression of CDC-47, VEGF, Flk-1 (VEGF receptor) and COX-2. Apoptosis was evaluated by the TUNEL assay. We assessed the gene expression of VEGF, Flk-1, caspase 3, COX-2 and PGF2? receptor using real time RT-PCR. The data were analyzed by SNK test. Results Hypothyroidism reduced COX-2 expression on day 10 and 19 (P?0.05), endothelial/pericyte and luteal cell proliferation on day 10 and 14 (p?0.05), apoptotic cell numbers on day 19 (p?0.05) and the expression of Flk-1 and VEGF on day 14 and 19, respectively (p?0.05). Hyperthyroidism increased the expression of COX-2 on day 19 (P?0.05) and the proliferative activity of endothelial/pericytes cells on day 14 (p <0.05), as well as the expression of VEGF and Flk-1 on day 19 (P?0.05). Conclusions Hypothyroidism reduces the proliferation, apoptosis and expression of angiogenic factors and COX-2in the corpus luteum of pregnant rats, contrary to what is observed in hyperthyroid animals, being this effect dependent of the gestational period.
Transplacental transmission of Toxoplasma gondii in reinfected pregnant female canines.
Twelve pregnant female canines, naturally infected with Toxoplasma gondii, were reinfected with T. gondii: three (GI) received tachyzoites subcutaneously (1.0 x 107), three (GII) were orally inoculated with oocysts (1.5 x 104), and six (GIII) were kept as a nonreinfected control group. All the reinfected female canines (GI and GII) miscarried or presented fetal death, while only one GIII female presented a stillborn in a litter of four pups (P < 0.01). Fever, lymphoadenopathy, miscarriage, and fetal death were the main clinical alterations observed. The highest serological titers detected through the indirect fluorescence antibody test (IFAT) were 1,024 (GI) and 4,096 (GII). In group III, the titers ranged between 64 and 256. By bioassays in mice, T. gondii was isolated in 17 organs of the reinfected adult canines, in 11 of the control group, and in 20 of the neonates. Positive immunostaining of cysts and/or tachyzoites were observed in 26 canine tissues (14 from GI and GII and ten from GIII). The agent was detected by immunohistochemistry in the encephalon of a neonate and in the spinal cord of a stillborn, thus, confirming that T. gondii infected canine fetuses, provoking miscarriages, even in bitches that presented primoinfection. PMID:19137327
Bresciani, K D S; Costa, A J; Toniollo, G H; Luvizzoto, M C R; Kanamura, C T; Moraes, F R; Perri, S H V; Gennari, S M
Multiple mating and its relationship to alternative modes of gestation in male-pregnant versus female-pregnant fish species
We construct a verbal and graphical theory (the "fecundity-limitation hypothesis") about how constraints on the brooding space for embryos probably truncate individual fecundity in male-pregnant and female-pregnant species in ways that should differentially influence selection pressures for multiple mating by males or by females. We then review the empirical literature on genetically deduced rates of multiple mating by the embryo-brooding parent in various fish species with three alternative categories of pregnancy: internal gestation by males, internal gestation by females, and external gestation (in nests) by males. Multiple mating by the brooding gender was common in all three forms of pregnancy. However, rates of multiple mating as well as mate numbers for the pregnant parent averaged higher in species with external as compared with internal male pregnancy, and also for dams in female-pregnant species versus sires in male-pregnant species. These outcomes are all consistent with the theory that different types of pregnancy have predictable consequences for a parent's brood space, its effective fecundity, its opportunities and rewards for producing half-sib clutches, and thereby its exposure to selection pressures for seeking multiple mates. Overall, we try to fit these fecundity-limitation phenomena into a broader conceptual framework for mating-system evolution that also includes anisogamy, sexual-selection gradients, parental investment, and other selective factors that can influence the relative proclivities of males versus females to seek multiple sexual partners.
Avise, John C.; Liu, Jin-Xian
The formation of gastric ulcer in pregnant and nonpregnant rats in the light of data on the gestation dominant
Summary Caffeine and arsenous acid were administered per os to pregnant and nonpregnant rats for a period of 15 to 19 days to induce gastric ulcer. The ulcerative process developed in 100% of the control, nonpregnant female rats; severe lesions with coalescence of small superficial ulcers into large, and involvement of all the gastric layers in the process, were observed
V. D. Rozanova; I. A. Arshavskii
The immunomodulatory effects induced by dietary Zearalenone in pregnant rats.
Abstract Context: Zearalenone (ZEN) is a common contaminant that is present in feedstuff of high humidity and high temperatures. Objective: The aim of this study was to investigate the effects of diets contaminated with different concentrations of ZEN on immunomodulation in early pregnant rats. Materials and methods: Forty-eight pregnant Sprague Dawley (SD) rats were randomly divided into four treatment groups fed on a diet supplemented with one of four concentrations of ZEN: 0?mg/kg (ZEN 0), 50?mg/kg (ZEN 50), 100?mg/kg (ZEN 100) and 150?mg/kg (ZEN 150). The pregnant rats were fed ZEN-treated diets from gestation days 0 to 7 and a basal diet from gestation days 8 to 20. Results: ZEN exposure (ZEN 100 and 150) caused significant decreases in splenic coefficients, viability of splenocyte and T-cell proliferation and induced histopathological damage in the spleen of early pregnant rats compared with other groups. Levels of IgG and IgA were decreased, while IgM was increased, in high doses of ZEN (ZEN 100 and ZEN 150) compared with other groups. ZEN 150 caused increases in white blood cells and hemoglobin and induced a significant decrease in platelets in blood of the pregnant rats compared with other groups. ZEN 150 increased the mRNA expression levels of interleukin (IL)-6, IL-18 and IL-1? and decreased the mRNA expression levels of interferon-?, tumor necrosis factor-? and IL-10 in the spleen of pregnant rats compared with ZEN 0. Conclusion: High doses of ZEN-induced immunomodulatory effects on early pregnant rats by altering immunological parameters. PMID:24754511
Yin, Shutong; Zhang, Yuanyuan; Gao, Rui; Cheng, Baojing; Shan, Anshan
The purpose of this study was to evaluate the teratogenic potential of Imidan in Wistar rats. Accordingly, groups of pregnant Wistar rats received Imidan by either a single or multiple dose protocol and their fetuses were examined for gross, soft tissue, and skeletal defects. In ...
Loss of acute satiety response to cholecystokinin in pregnant rats.
During pregnancy, food intake and fat mass are increased to meet the energy demands of the growing conceptus and to prepare for the subsequent demands of lactation. A state of leptin resistance develops during pregnancy in the rat, which can facilitate the increase in food intake despite pregnancy-induced increases in leptin concentrations. Cholecystokinin (CCK) is a satiety factor that is released from the gut during feeding and acts to terminate short-term food intake. Circulating leptin concentrations can modulate the anorexic response to CCK; low leptin concentrations decrease the potency of CCK to reduce food intake. Because rats are leptin resistant by day 14 of pregnancy, it was hypothesised that the feeding response to CCK would be attenuated at that time. Nonpregnant and day 14 pregnant rats received an i.p. injection of CCK-8 (3 ?g/kg body weight) or vehicle directly before the start of the dark phase. Food intake was measured 30 min after lights out. Approximately 90 min after receiving either CCK-8 or vehicle, rats were transcardially perfused with 4% paraformaldehyde. Food intake was significantly decreased in CCK-treated nonpregnant rats, although similar treatment did not reduce food intake in day 14 pregnant rats. CCK treatment lead to significant increased in c-Fos expression in the nucleus of the solitary tract (NTS) in both nonpregnant and pregnant rats compared to vehicle treatment, although the number of CCK-induced c-Fos positive cells was significantly less in pregnant rat compared to nonpregnant rats. Although CCK treatment increased the number of c-Fos positive cells in the hypothalamic paraventricular nucleus and supraoptic nucleus in nonpregnant rats, no significant increase was observed in these areas during pregnancy. These results indicate that pregnant rats are no longer responsive to the actions of CCK on short-term food intake and that CCK action in the NTS is reduced during pregnancy. PMID:21771116
Ladyman, S R; Sapsford, T J; Grattan, D R
[Effects of cold on triiodothyronine metabolism in the pregnant rat].
Sixteen Wistar rats were studied in the last week of pregnancy. Another group of 6 nonpregnant animals served as control. Eight pregnant and 6 control ratas were kept in the cold room at 4 degrees C for 4 days, while 8 pregnant rats remained at 22 degrees C. After blocking the thyroid gland with potassium perchlorate to prevent iodine reutilization, a dose of 4 microCi of 125I-T3 was injected i.p. Thereafter, animals were placed in individual metabolic cages for separate 24 h collection of urine and feces. Heparinized blood samples were obtained at 4, 14, 24 and 28 h following tracer injection. Pregnant rats exposed to cold had a significant increase in T3 fractional turnover as compared to pregnants at 22 degrees C (p < 0.005) and to controls at 4 degrees C (p < 0.02). No changes were observed in space of distribution, serum concentration and body pool of T3. Degradation of this hormone, however, was significantly augmented (p < 0.05) in pregnants at 4 degrees C as compared to pregnants at 22 degrees C, although not when compared to controls at 4 degrees C. The urinary excretion of 125I was increased in pregnants in the cold (p <0.005) versus pregnants at 22 degrees C. The metabolic (p < 0.005), urinary (p < 0.001) and fecal (p < 0.05) clearances in pregnants at 4 degrees C were augmented with respect to the other two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7476108
Blanco, M R; Cageao, L; Rivera, O E; Belmonte, N; Zaninovich, A A
Mortality associated with using medetomidine and ketamine for general anesthesia in pregnant and nonpregnant Wistar rats.
Medetomidine and ketamine are injectable drugs that can be used in combination to induce general anesthesia in rats. After noticing a high incidence of morbidity and mortality in pregnant Wistar rats given medetomidine and ketamine for anesthesia, the authors further investigated the effects of this combination of anesthetic drugs in both pregnant and nonpregnant Wistar rats. The time to recumbency and the duration of general anesthesia were similar between pregnant and nonpregnant rats. Pregnancy status did not affect the rats' pulse rate, respiratory rate, rectal temperature, oxygen saturation or perfusion index during 2 h of anesthesia. Pregnant rats had significantly lower blood glucose concentrations than nonpregnant rats at all time points, though blood glucose concentrations increased in both groups. The mortality rate was ?15% both for nonpregnant rats and for pregnant rats. Researchers using medetomidine and ketamine to anesthetize Wistar rats should carefully monitor the rats in order to minimize mortality. PMID:24845007
Callahan, Lauren M; Ross, Simone M; Jones, Megan L; Musk, Gabrielle C
Methodological differences account for inconsistencies in reported free VEGF concentrations in pregnant rats.
Free vascular endothelial growth factor (VEGF) is undetectable in plasma during human pregnancy. However, studies examining pregnant rats have reported both low (8-29 pg/ml) and high (527-1,030 pg/ml) free VEGF. These discrepancies cast uncertainty over the use of rat models to study angiogenic factors in pregnancy and preeclampsia. This study investigates methodological factors that may explain these discrepancies. Plasma VEGF in nonpregnant, day 7 pregnant, and day 19 pregnant rats was measured using rat and mouse ELISAs (R&D Systems). The rat ELISA detected VEGF in plasma from nonpregnant rats but not in plasma from day 19 pregnant rats. The mouse ELISA detected higher VEGF concentrations than the rat ELISA in every sample tested. This discrepancy was greater in day 19 pregnant rats (median: 2,273 vs. 0 pg/ml) than in nonpregnant (97 vs. 20 pg/ml) and day 7 pregnant (66 vs. 2 pg/ml) rats. Recovery of recombinant rat VEGF (rrVEGF) spiked into plasma from nonpregnant and day 7 pregnant rats was high for the rat ELISA (82-105%) but low for the mouse ELISA (17-22%). The rat ELISA did not recover rrVEGF in plasma from day 19 pregnant rats, suggesting that this ELISA measures free VEGF. The use of the rat versus mouse ELISA likely explains the differences in reported VEGF concentrations in pregnant rats. While the rat ELISA appears to measure free VEGF, plasma concentrations in nonpregnant and pregnant rats are below the assay sensitivity limit. As most previous studies of pregnant rats used the mouse VEGF ELISA, these data should be interpreted cautiously. PMID:24622973
Weissgerber, Tracey L; McConico, Andrea; Knudsen, Bruce E; Butters, Kim A; Hayman, Suzanne R; White, Wendy M; Milic, Natasa; Miller, Virginia M; Garovic, Vesna D
Effect of Bauhinia forficata extract in diabetic pregnant rats: maternal repercussions.
Bauhinia forficata, commonly known as "paw-of-cow", is widely used in Brazil folk medicine for the treatment of Diabetes mellitus. The purposes of present study were to determine the repercussions of diabetes on the defense system against oxidative stress in pregnant female rats and to characterize the influence of the treatment with Bauhinia forficata extract on the antioxidant system, glycemic control, hepatic glycogen, cholesterol, triglycerides, total proteins and lipids. Virgin female Wistar rats were injected with 40 mg/kg streptozotocin (STZ) before mating. Oral administration of an aqueous extract of Bauhinia forficata leaves was given to non-diabetic and diabetic pregnant rats in 3 doses: 500 mg/kg from 0 to 4th day of pregnancy, 600 mg/kg from 5th to 14th day and 1000 mg/kg from 15th to 20th day. All the females were killed on the day 21 of pregnancy. A maternal blood sample was collected by venous puncture and the maternal liver was removed for biochemical measurement. The diabetic pregnant rats presented hyperglycemia, hyperlipemia, hypertriglyceridemia, hypercholesterolemia, hyperuricemia, decreased determinations of reduced glutathione (GSH) and superoxide dismutase (SOD). Treatment with B. forficata extract did not interfere in the albumin, total protein and lipid, triglyceride, cholesterol and SOD determinations. Increased hepatic glycogen, decreased uric acid concentration and increased GSH activity was observed. This last fact suggests that the plant may have some action on antioxidant defense system. However, the demonstration of the active component present in B. forficata responsible for its antioxidant effect and the increase in hepatic glycogen deserve further investigation. PMID:15070172
Damasceno, D C; Volpato, G T; Calderon, I de Mattos Paranhos; Aguilar, R; Rudge, M V Cunha
Daily indium chloride doses of control (0) or 200 mg\\/kg were administered orally to pregnant Sprague-Dawley (SD) rats by gavage, on d 6-15 of gestation. On d 16 of gestation hemodynamic tests were performed; Arterial blood pressure, cardiac output (CO), and volume organ blood flow were determined with radioactive microspheres using the reference sample method (McDevitt & Nies, 1976). Indium
Veronika Morvai; György Ungváry; Éva Szakmáry
Stress-Induced Proteomic Changes in the Hippocampus of Pregnant Wistar Rats
Stress is a threatening factor that all living organisms encounter throughout life. Depending on the type of stress, there are several mechanisms for keeping body homeostasis to minimize stress effects. Brain is an organ which shows high sensitivity to stress conditions. Although many studies have shown induced-stress effects on rat embryos, little is known about the mechanisms involved in coping with stress by female rats during pregnancy. In the present study, restraint stress method was applied because this technique has been widely used in animal models to induce both psychological and physical stress. Restraint stress was applied in regular sessions (1 and 3 hrs) in two groups of 6 pregnant Wistar rats and similar number of animals was used as control group receiving no stress. ACTH and corticosterone levels in plasma samples were shown to increase in response to stress treatments. On the last day of pregnancy, rat hippocampus from the brain of each animal in all three groups was removed and analyzed using 2 Dimensional Gel Electrophoresis (2DE) technique. Using Image Master Software, approximately 2000 proteins were detected in the 2D gels analyzed, among which 34 proteins exhibited differential expression. These results indicate that the proteome patterns from the hippocampus of pregnant rats subjected to 1 and 3 hr of stress differs significantly from the control (unstressed) group. Future mass spectrometry identification of the 34 protein spots discovered in this study should allow a more precise understanding of molecules and cellular pathways involved in stress-induced responses during pregnancy.
Ardekani, Ali M.; Maghsudi, Nader; Meyfour, Anna; Ghasemi, Rasool; Lakpour, Niknam; Nooshinfar, Elahe; Ghaempanah, Zahra
Mercury 203 distribution in pregnant and nonpregnant rats following systemic infusions with thiol-containing amino acids
Near-term pregnant (gestational day 17) and nonpregnant Long-Evans female rats were continuously infused into the external jugular vein with 0.1 mmole/hour L-cysteine, 0.1 mmole/hour L-leucine, or saline. At 24, 48, and 72 hours, 50 mumole/hour (/sup 203/Hg)-MeHgCl was administered over 1 hour. Total /sup 203/Hg body burden, brain, kidney, liver, and blood /sup 203/Hg concentrations were determined at 96 hours by gamma scintillation spectrometry. Despite significantly greater /sup 203/Hg whole body retention in the pregnant animals /sup 203/Hg concentrations in blood, brain, kidney, and liver were higher in nonpregnant rats. In addition, brain /sup 203/Hg concentrations in both pregnant and virgin rats were significantly higher in L-cysteine-treated rats compared with controls. These results suggest that the fetus may act as a sink for MeHg, thus decreasing /sup 203/Hg concentrations in maternal blood, brain, kidney, and liver. Furthermore, the data indicate that brain uptake of methylmercury in both pregnant and nonpregnant rats is enhanced by chronic L-cysteine infusion, lending support to the hypothesis that methylmercury in the rat may be translocated across the blood-brain barrier by the neutral amino acid carrier transport system.
Aschner, M.; Clarkson, T.W.
Influence of treatment with quercetin on lipid parameters and oxidative stress of pregnant diabetic rats.
Among the numerous coadjuvant therapies that could influence the incidence and progression of diabetic complications, antioxidants and flavonoids are currently being tested in clinical trials. We investigated the effect of quercetin on biochemical parameters in streptozotocin-induced (60 mg/kg body mass, by intraperitoneal injection) diabetic rats. A total of 32 female Wistar rats were distributed among 4 groups as follows: control (G1); control treated with quercetin (G2); diabetic (G3); and diabetic treated with quercetin (G4). Quercetin administered to pregnant diabetic rats controlled dyslipidemia and improved lipid profiles in diabetes mellitus, regulated oxidative stress by reducing the generation of lipid hydroperoxides, and increased the activity of the antioxidant enzyme glutathione peroxidase. PMID:23458202
Pereira Braga, Camila; Momentti, Ana Carolina; Barbosa Peixoto, Fernando; de Fátima Ferreira Baptista, Rafaela; dos Santos, Felipe André; Fava, Fábio Henrique; Fernandes, Ana Angélica Henrique
Round ligament lipoma mimicking acute appendicitis in a 24-week pregnant female: a case report.
An exhaustive search of the literature using the Pub Med database revealed no reports of round ligament lipomas mimicking acute appendicitis in pregnant patients. There are relatively few articles on round ligament lipomas and even less on round ligament lipomas during pregnancy. This case report is on a 27-year-old 24-week pregnant female who presented with signs and symptoms similar to acute appendicitis who in fact had a large right pelvic round ligament lipoma that was causing her pain. PMID:21786146
Miller, T J; Paulk, D G
Acute effects of thymoquinone on the pregnant rat and embryo-fetal development.
The effect of a single intraperitoneal (i.p.) injection of thymoquinone (TQ) on the pregnant rat and embryo-fetal development was investigated. Pregnant female Wistar rats received 15, 35, and 50 mg/kg body weight of TQ i.p. on day 11 or 14 of gestation, and on day 18 of gestation they were sacrificed and laparotomized. Results showed that TQ induces maternal and embryonic toxicities in a dose- and time-dependent manner. With a dose of 50 mg/kg, treated rats experienced a significant decrease in maternal body weight and complete fetal resorption when the dose was given on day 11 of gestation. On the other hand, 46.2% of implants were resorbed and the viable fetuses showed no TQ-related malformations when the dose was given on day 14 of gestation. At a lower TQ dose of 35 mg/kg, maternal and embryonic toxicities were observed only when it was given on day 11 of gestation. The dose of 15 mg/kg was considered to be a dose with no observed adverse effect level for maternal and embryo-fetal toxicities when it was given day 11 or 14 of gestation. Based on the results of this study, TQ, at doses of 50 and 35 mg/kg, has a potentially disruptive effect on embryonic development during the second trimester of rat pregnancy. PMID:22360537
AbuKhader, Majed M; Khater, Samar H; Al-Matubsi, Hisham Y
Factors associated with antenatal depression in pregnant Korean females: the effect of bipolarity on depressive symptoms
Background This cross-sectional study sought to identify factors associated with antenatal depression in pregnant Korean females, including sociodemographic parameters, social support, social conflict, and bipolarity. Methods Eighty-four pregnant women were recruited to complete questionnaires on sociodemographic factors, obstetric history, depressive symptoms, and bipolarity. Depressive symptoms were assessed using the Korean version of the Edinburgh Postnatal Depression Scale. Bipolarity was assessed using the Korean version of the Mood Disorder Questionnaire. Results Nineteen participants (22.6%) had positive Mood Disorder Questionnaire scores, suggesting the presence of bipolarity, and were significantly more likely to score high on the Edinburgh Postnatal Depression Scale. Antenatal depression was associated with bad marital communication and marital dissatisfaction. Conclusion These results suggest that spousal interactions play a significant role in antenatal depression, and pregnant women with bipolarity may be more depressed than those without bipolarity.
Park, Chul Min; Seo, Hye-Jin; Jung, Young-Eun; Kim, Moon-Doo; Hong, Seong-Chul; Bahk, Won-Myong; Yoon, Bo-Hyun; Hur, Min Hee; Song, Jae Min
A BBDR-HPT Axis Model for the Pregnant Rat and Fetus: Evaluation of Iodide Deficiency
A biologically based dose response (BBDR) model for the hypothalamic-pituitarythyroid (HPT) axis for the pregnant rat and fetus is being developed to advance understanding of thyroid hormone disruptions and developmental neurotoxicity (DNT). The model for the pregnant rat and fet...
Brain oxytocin: differential inhibition of neuroendocrine stress responses and anxiety-related behaviour in virgin, pregnant and lactating rats
The involvement of brain oxytocin in the attenuated responsiveness of the hypothalamo-pituitary–adrenal axis and the oxytocin systems to external stressors found in pregnant and lactating rats has been studied, including both neuroendocrine and behavioural aspects. Intracerebroventricular infusion of an oxytocin receptor antagonist (0.75?g\\/5?l), but not of vehicle, elevated basal corticotropin and corticosterone secretion into blood of virgin female, but not
I. D. Neumann; L. Torner; A. Wigger
Atrazine (ATR) is a widely used herbicide shown to delay early mammary development in female offspring of gestationally exposed rats. The effects of ATR can be induced by in utero exposure and/or suckling from a dam exposed during late pregnancy, but ATR is reported to have a hal...
Polyaromatic compounds alter placental protein synthesis in pregnant rats
The administration of the polyaromatic compounds {beta}-naphthoflavone ({beta}NF) and 3-methylcholanthrene (3MC) to pregnant rats during mid-gestation has been shown to produce marked feto-placental growth retardation. This study examined secretory protein synthesis in placental tissue from rats following administration of {beta}NF on gestation days (gd) 11-14 or 3MC on gd 12-14. Explants of placental basal zone tissue were cultured for 24 hours in serum-free medium in the presence of ({sup 3}H)leucine. Secreted proteins were analyzed by two-dimensional SDS-polyacrylamide gel electrophoresis followed by either fluorography or immunostaining. Total incorporation of ({sup 3}H)leucine into secreted proteins was not altered in BZ explants from {beta}NF or 3MC-treated animals. However a selective decrease was observed in ({sup 3}H)leucine incorporation into a major complex of proteins with apparent molecular weight of 25-30,000 and isoelectric point between 5.3 to 5.7. This group of proteins has been further identified as being related to rat pituitary growth hormone (GH) using N-terminal amino acid microsequencing of individual spots from 2-D SDS-PA gels. This is the first report that synthesis of GH-related proteins by rat placenta is decreased following {beta}NF and 3MC administration, a change which may underlie the feto-placental growth retardation associated with these polyaromatic compounds.
Shiverick, K.T.; Ogilvie, S.; Medrano, T. (Univ. of Florida, Gainesville (United States))
Pharmacokinetics of puerarin in pregnant rats at different stages of gestation after oral administration.
This study aims to observe the effects of gestational stage on the pharmacokinetics of puerarin after oral administration in rats. The pharmacokinetics of puerarin was studied in pregnant rats using a sensitive and reproducible high-performance liquid chromatography/ultraviolet method. The concentration-time curves in both normal and pregnant rats were fit into a two-compartment model. The results indicated that gestation influences the pharmacokinetics of puerarin at different levels, especially during the early stages of pregnancy. Furthermore, puerarin penetrates the placental barrier and maintains high concentrations in fetal rat plasma. Therefore, puerarin administration should be carefully considered in pregnant women. PMID:23500385
Cao, Li; Pu, Jie; Cao, Qing-Ri; Chen, Bo-Wen; Lee, Beom-Jin; Cui, Jing-Hao
Is embryonic mortality increased in normal female rats mated to subfertile males?
Normal female rats were mated to control males or males which were subjected to unilateral testicular heating (43 degrees C for 30 min), irradiation (500 R), efferent duct ligation, arterial ligation or castration; in all males, the contralateral ductus deferens was ligated. All treatments caused reduced fertility and eventually infertility, as judged by the percentage of females becoming pregnant; the infertility was temporary after heating and irradiation. During the periods of reduced fertility, the numbers of fetuses per pregnant female and the fetus/corpus luteum ratios were reduced. In subsequent experiments, after heating of the testis, there was not only failure of fertilization despite the presence of normal numbers of spermatozoa in the uterus, but also an increased rate of embryonic degeneration in normal females. These results provide evidence that the male, while still fertile, can affect the fecundity of the female and the rate of embryo mortality. PMID:3361491
Setchell, B P; D'Occhio, M J; Hall, M J; Laurie, M S; Tucker, M J; Zupp, J L
The UF Family of hybrid phantoms of the pregnant female for computational radiation dosimetry.
Efforts to assess in utero radiation doses and related quantities to the developing fetus should account for the presence of the surrounding maternal tissues. Maternal tissues can provide varying levels of protection to the fetus by shielding externally-emitted radiation or, alternatively, can become sources of internally-emitted radiation following the biokinetic uptake of medically-administered radiopharmaceuticals or radionuclides located in the surrounding environment-as in the case of the European Union's SOLO project (Epidemiological Studies of Exposed Southern Urals Populations). The University of Florida had previously addressed limitations in available computational phantom representation of the developing fetus by constructing a series of hybrid computational fetal phantoms at eight different ages and three weight percentiles. Using CT image sets of pregnant patients contoured using 3D-DOCTOR(TM), the eight 50th percentile fetal phantoms from that study were systematically combined in Rhinoceros(TM) with the UF adult non-pregnant female to yield a series of reference pregnant female phantoms at fetal ages 8, 10, 15, 20, 25, 30, 35 and 38?weeks post-conception. Deformable, non-uniform rational B-spline surfaces were utilized to alter contoured maternal anatomy in order to (1) accurately position and orient each fetus and surrounding maternal tissues and (2) match target masses of maternal soft tissue organs to reference data reported in the literature. PMID:25030913
Maynard, Matthew R; Long, Nelia S; Moawad, Nash S; Shifrin, Roger Y; Geyer, Amy M; Fong, Grant; Bolch, Wesley E
The effects of spaceflight on mammary metabolism in pregnant rats
NASA Technical Reports Server (NTRS)
The effects of spaceflight on mammary metabolism of 10 pregnant rats was measured on Day 20 of pregnancy and after parturition. Rats were flown on the space shuttle from Day 11 through Day 20 of pregnancy. After their return to earth, glucose oxidation to carbon dioxide increased 43% (P < 0.05), and incorporation into fatty acids increased 300% (P < 0.005) compared to controls. It is unclear whether the enhanced glucose use is due to spaceflight or a response to landing. Casein mRNA and gross histology were not altered at Day 20 of pregnancy. Six rats gave birth (on Day 22 to 23 of pregnancy) and mammary metabolic activity was measured immediately postpartum. The earlier effects of spaceflight were no longer apparent. There was also no difference in expression of beta-casein mRNA. It is clear from these studies that spaceflight does not impair the normal development of the mammary gland, its ability to use glucose, nor the ability to express mRNA for a major milk protein.
Plaut, K.; Maple, R.; Vyas, C.; Munaim, S.; Darling, A.; Casey, T.; Alberts, J. R.
Biotransformation of 2,3,3,3-tetrafluoropropene (HFO-1234yf) in male, pregnant and non-pregnant female rabbits after single high dose inhalation exposure.
2,3,3,3-Tetrafluoropropene (HFO-1234yf) is a novel refrigerant intended for use in mobile air conditioning. It showed a low potential for toxicity in rodents studies with most NOAELs well above 10,000 ppm in guideline compliant toxicity studies. However, a developmental toxicity study in rabbits showed mortality at exposure levels of 5,500 ppm and above. No lethality was observed at exposure levels of 2,500 and 4,000 ppm. Nevertheless, increased subacute inflammatory heart lesions were observed in rabbits at all exposure levels. Since the lethality in pregnant animals may be due to altered biotransformation of HFO-1234yf and to evaluate the potential risk to pregnant women facing a car crash, this study compared the acute toxicity and biotransformation of HFO-1234yf in male, female and pregnant female rabbits. Animals were exposed to 50,000 ppm and 100,000 ppm for 1h. For metabolite identification by (19)F NMR and LC/MS-MS, urine was collected for 48 h after inhalation exposure. In all samples, the predominant metabolites were S-(3,3,3-trifluoro-2-hydroxypropanyl)-mercaptolactic acid and N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-L-cysteine. Since no major differences in urinary metabolite pattern were observed between the groups, only N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-L-cysteine excretion was quantified. No significant differences in recovery between non-pregnant (43.10 ± 22.35 ?mol) and pregnant female (50.47 ± 19.72 ?mol) rabbits were observed, male rabbits exposed to 100,000 ppm for one hour excreted 86.40 ± 38.87 ?mol. Lethality and clinical signs of toxicity were not observed in any group. The results suggest that the lethality of HFO-1234yf in pregnant rabbits unlikely is due to changes in biotransformation patterns or capacity in pregnant rabbits. PMID:22664346
Schmidt, Tobias; Bertermann, Rüdiger; Rusch, George M; Hoffman, Gary M; Dekant, Wolfgang
Placental transport of vitamin B12 in the pregnant rat
Placental transport of vitamin B12 was studied in the pregnant rat in two series of experiments. In the first series animals were given cyanocobalamin-57Co intravenously at various stages of gestation. High specific activity tracer was used and doses of B12 were 1-2 ng per animal. The rats were killed from 15 min to 24 hr after injection and the fetuses, placentas, and serum were assayed for radioactivity. In the second series using uninjected animals, absolute amounts of vitamin B12 in fetuses and placentas were measured at stages of gestation from day 12 through day 20. There was a progressive increase in B12 transferred to the fetus during gestation. Although the quantity of vitamin B12 transported per 24 hr was proportional to fetal weight, the amount transported per gram of placenta increased tenfold from day 10 through day 19. Uptake of tracer B12 by placenta was initially rapid; however, no radioactivity appeared in the fetus until 2 hr after injection. The actual amount of B12 in placenta increased throughout gestation, and the placental concentration of B12 was greater than maternal plasma and fetal tissue concentrations at all times measured. These data suggest that the ability of placenta to transport B12 increased throughout gestation, and that the rate-limiting step in the transport process was either the passage of B12 from the maternal to the fetal side of placenta or the transfer from placenta into fetal plasma.
Graber, Stanley E.; Scheffel, Ursula; Hodkinson, Barbara; McIntyre, Patricia A.
Cadmium toxicity in the thyroid gland of pregnant rats
The toxic effects of cadmium on the thyroid gland of pregnant rats were studied with an electron microscope and an X-ray microanalyzer. Serum levels of thyroid hormones (T3 and T4) were also analyzed. Deterioration of the rough-surfaced endoplasmic reticulum occurred in the thyroid follicular epithelium on the fifth day of cadmium treatment. Large intracellular vacuoles, which arose from dilated cisternae of the rough-surfaced endoplasmic reticulum, were fused together, and marked swelling of the mitochondria was also noted. Thyroglobulin-secreting granules at the apical cytoplasm were decreased in number. By energy dispersive X-ray microanalysis, cadmium peaks were preferentially obtained from swollen mitochondria in the follicular epithelial cells. Serum levels of T3 and T4 were significantly decreased in cadmium-treated rats dams when compared to those of controls. In the present experiment, cycloheximide also caused degenerative changes in the rough-surfaced endoplasmic reticulum and the disappearance of thyroglobulin-secreting granules. Cycloheximide is a known inhibitor of protein synthesis on cytosolic ribosomes. These results indicated that accumulated cadmium in the mitochondria of thyroid follicular epithelial cells might disturb the oxidative phosphorylation of this organelle and the loss of energy supply possibly caused the inhibition of the synthesis and release of thyroid hormones.
Yoshizuka, M.; Mori, N.; Hamasaki, K.; Tanaka, I.; Yokoyama, M.; Hara, K.; Doi, Y.; Umezu, Y.; Araki, H.; Sakamoto, Y. (Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, Kitakyushu (Japan))
Dual effects of melatonin on uterine myoelectrical activity of non-pregnant rats
Objective In this experimental study, we aimed to investigate the role of melatonin on uterine myoelectrical activity of non-pregnant rats. Material and Methods Forty-six female rats were assigned to six groups: (1) control; (0.2 mL 0.9% NaCl was injected intravenously (IV), n=6); (2) melatonin applied as 0.4 mg/kg/IV (n=8); (3) melatonin applied as 4 mg/kg/IV (n=8); (4) single dose of oxytocin (100 mU/kg) injected IV (n=8); (5) melatonin (0.4 mg/kg) plus oxytocin (100 mU/kg) (n=8); and (6) melatonin (4 mg/kg) plus oxytocin (100 mU/kg) injected IV (n=8). Each rat underwent a laparotomy, and uterine myoelectrical signals were recorded. The mean spectrum, averaged over the spectral content of signals in each group, was compared. Results Melatonin induced uterine myoelectrical activity in a dose-dependent manner. Treatment of melatonin after oxytocin suppressed the mean power of the signals. Serum melatonin concentrations were significantly higher in melatonin-treated rats. Conclusion Melatonin itself at two different dose levels was found to be equally effective in stimulating the uterine electrical signals, although oxytocin-induced uterine electrical activity was suppressed by melatonin. These findings merit further investigations on the possible beneficial role of melatonin in the treatment of conditions associated with abnormal uterine activity.
Simsek, Yavuz; Parlakp?nar, Hakan; Turhan, Ugur; Tagluk, Mehmet Emin; Ates, Burhan
Ivermectin reduces sexual behavior in female rats.
Ivermectin (IVM) is an antiparasitic drug that is widely used in domestic animals. In mammals, IVM acts as a ?-aminobutyric acid (GABA) receptor agonist. This neurotransmitter plays an important role in the regulation of female sexual behavior. The present study investigated the effects of therapeutic (0.2 mg/kg) and high (1.0 mg/kg) IVM doses on female sexual behavior in physiological and pharmacological conditions. Female rats in estrus or treated with estradiol valerate to induce sexual behavior 24 h before the experiments were used. Ivermectin was administered 15 min before the sexual observations. The number of lordosis events in 10 mounts was recorded to calculate the lordosis quotient. The intensity of lordosis (0 [no lordosis], 1 [low lordosis], 2 [normal lordosis] and 3 [exaggerated lordosis]) was scored. In estrus and hormonal treated female rats, both IVM doses decreased the intensity of the lordosis reflex and the percentage of females that presented high levels of lordosis (exaggerated lordosis). However, the number of females that presented lordosis was unaltered. We conclude that in both hormonal conditions, 0.2mg/kg IVM treatment reduced female sexual behavior and the execution of the lordosis reflex. The present results may be useful for avoiding the side effects of this drug in veterinary practice. PMID:24681284
Moreira, N; Bernardi, M M; Spinosa, H S
Baccharis trimera: Effect on hematological and biochemical parameters and hepatorenal evaluation in pregnant rats
Aim of the studyThis investigation evaluated the effect of a hydroethanolic extract of Baccharis trimera on pregnant Wistar rats, once the plant is well-known consumed in pregnancy and little is known on its potentially toxic effects on pregnant women.
Simone Reschke Mendes Grance; Maria Araújo Teixeira; Roseana Silveira Leite; Eurípedes Batista Guimarăes; Joăo Máximo de Siqueira; Wander Fernando de Oliveira Filiu; Simone Bertozi de Souza Vasconcelos; Maria do Carmo Vieira
Susceptibility of fetal, virgin, pregnant and lactating rats for the induction of mammary tumors by gamma rays
Pregnant Wistar-MS rats received a whole-body irradiation of 0-2.6 Gy {gamma} rays at day 20 of pregnancy. The mother rats were implanted with a diethylstilbestrol (DES) pellet 30 days after weaning, and the female pups delivered by the irradiated mother were treated with DES after maturation. Lactating rats were irradiated with {gamma} rays 21 days after parturition and then treated with DES. Virgin rats 70 days of age were also irradiated and then administered DES. The rats which received intrauterine irradiation did not develop mammary tumors in the mother rats and lactating rats increased in a dose-dependent manner with increasing doses of {gamma} rays up to 2.1 Gy. With 0.1-1 Gy, the incidence of adenocarcinoma in the mother rats was significantly lower than that observed in the lactating rats. However, the incidence in the mother rats irradiated with 1.0-1.5 Gy was significantly higher than that of virgin rats treated with the corresponding {gamma}-ray doses. These findings suggest that the susceptibility of the mammary glands to radiation depends upon the differentiation at the time of exposure. 22 refs., 4 figs., 2 tabs.
Inano, Hiroshi; Suzuki, Heiko; Onoda, Makoto; Yamanouchi, Hiroshi [National Institute of Radiological Sciences, Inage-ku, Chiba-shi (Japan)
The elimination, distribution, and metabolism of /sup 14/C-toxaphene in the pregnant rat
Pregnant Sprague-Dawley rats were orally administered /sup 14/C-toxaphene in olive oil on day 15 of pregnancy and housed in glass metabolism cages. Urine, feces, and tissues were collected and assayed for radioactivity. The elimination was similar to that in virgin females with the majority of activity excreted in the feces (38.4%; five days) and less in the urine (23.7%; five days). The fetuses contained the lowest levels of radioactivity of all tissues tested (28 ppb; five days) and fat contained the highest levels (7476 ppb; five days). A comparison of the activity in the fetuses with that in the dam's fat showed slight differences, indicating the presence of more polar compounds (perhaps metabolites).
Pollock, G.A.; Hillstrand, R.
Reproductive effects of butyl benzyl phthalate in pregnant and pseudopregnant rats
In our previous studies, butyl benzyl phthalate (BBP) was found to be embryolethal and teratogenic in rats. In this study, the reproductive effects of BBP were investigated in pregnant and pseudopregnant rats. Rats were given BBP by gastric intubation at 0, 250, 500, 750, or 1000 mg\\/kg on Days 0 to 8 of pregnancy and the pregnancy outcome was determined
Makoto Ema; Emiko Miyawaki; Kunio Kawashima
Biotransformation of 2,3,3,3-tetrafluoropropene (HFO-1234yf) in male, pregnant and non-pregnant female rabbits after single high dose inhalation exposure
2,3,3,3-Tetrafluoropropene (HFO-1234yf) is a novel refrigerant intended for use in mobile air conditioning. It showed a low potential for toxicity in rodents studies with most NOAELs well above 10,000 ppm in guideline compliant toxicity studies. However, a developmental toxicity study in rabbits showed mortality at exposure levels of 5,500 ppm and above. No lethality was observed at exposure levels of 2,500 and 4,000 ppm. Nevertheless, increased subacute inflammatory heart lesions were observed in rabbits at all exposure levels. Since the lethality in pregnant animals may be due to altered biotransformation of HFO-1234yf and to evaluate the potential risk to pregnant women facing a car crash, this study compared the acute toxicity and biotransformation of HFO-1234yf in male, female and pregnant female rabbits. Animals were exposed to 50,000 ppm and 100,000 ppm for 1 h. For metabolite identification by {sup 19}F NMR and LC/MS-MS, urine was collected for 48 h after inhalation exposure. In all samples, the predominant metabolites were S-(3,3,3-trifluoro-2-hydroxypropanyl)-mercaptolactic acid and N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-L-cysteine. Since no major differences in urinary metabolite pattern were observed between the groups, only N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-L-cysteine excretion was quantified. No significant differences in recovery between non-pregnant (43.10 ± 22.35 ?mol) and pregnant female (50.47 ± 19.72 ?mol) rabbits were observed, male rabbits exposed to 100,000 ppm for one hour excreted 86.40 ± 38.87 ?mol. Lethality and clinical signs of toxicity were not observed in any group. The results suggest that the lethality of HFO-1234yf in pregnant rabbits unlikely is due to changes in biotransformation patterns or capacity in pregnant rabbits. -- Highlights: ? No lethality and clinical signs were observed. ? No differences in metabolic pattern between pregnant and non-pregnant rabbits. ? Rapid and similar metabolite excretion in all groups. ? Very low amount of biotransformation in all groups (< 0.1%).
Schmidt, Tobias [Institut für Toxikologie, Universität Würzburg, Versbacher Str. 9, 97078 Würzburg (Germany)] [Institut für Toxikologie, Universität Würzburg, Versbacher Str. 9, 97078 Würzburg (Germany); Bertermann, Rüdiger [Institut für Anorganische Chemie, Universität Würzburg, Am Hubland, 97074 Würzburg (Germany)] [Institut für Anorganische Chemie, Universität Würzburg, Am Hubland, 97074 Würzburg (Germany); Rusch, George M. [Honeywell, P.O. Box 1057, Morristown, NJ 07962–1057 (United States)] [Honeywell, P.O. Box 1057, Morristown, NJ 07962–1057 (United States); Hoffman, Gary M. [Huntingdon Life Sciences., East Millstone, NJ (United States)] [Huntingdon Life Sciences., East Millstone, NJ (United States); Dekant, Wolfgang, E-mail: firstname.lastname@example.com [Institut für Toxikologie, Universität Würzburg, Versbacher Str. 9, 97078 Würzburg (Germany)] [Institut für Toxikologie, Universität Würzburg, Versbacher Str. 9, 97078 Würzburg (Germany)
Teratogenicity of Mimosa tenuiflora seeds to pregnant rats.
Bone and other malformations caused by the ingestion of Mimosa tenuiflora are common in ruminants in the Brazilian semiarid. The aim of this research was to study the teratogenic effects of M. tenuiflora in Wistar rats (Rattus novergicus). The experimental group had 15 females and was fed, from the 6th to the 21st day of pregnancy, with a ration containing 10% of M. tenuiflora seeds. The control group, with 10 females, was fed with the same ration without seeds. There were no differences in weight gains, and food and water consumption between treated and control rats. Ninety bone malformations were observed in 40 of the 101 fetuses born in the experimental group, and four malformations were observed in three of the 58 fetuses born in the control group (p<0.05). The weight and number of ossification centers of the fetuses from the experimental group were higher than those from the control group (p<0.05). It is concluded that the seeds of M. tenuiflora are teratogenic to rat fetuses. PMID:18078971
Medeiros, R M T; de Figueiredo, A P M; Benício, T M A; Dantas, F P M; Riet-Correa, F
Green Tea Extract Increases mRNA Expression of Enzymes Which Influence Epigenetic Marks in Newborn Female Offspring from Undernourished Pregnant Mother
Biochemical and toxicological properties of catechin remain unclear, e.g.; how catechin affects female offspring from undernourished pregnant dams. Here, to elucidate effects of low prenatal protein on female offspring health status, changes of enzymes which modify epigenetic marks related with metabolism in kidneys from newborns were investigated after continuously administering catechin extracted from green tea to lactating maternal rats after pregnant undernourishment. We found that green tea extract intake during lactation up-regulated the activation of AMP-activated protein kinase in young female offspring from protein-restricted dams and modulated the AMP-activated protein kinase pathway in the kidney. This pathway was indicated to be stimulated by SIRT1 gene expression. The feeding of green tea extract to protein-restricted dams during lactation is likely to up-regulate AMP-activated protein kinase activation and may partly lead to alterations of the AMP-activated protein kinase pathway in female offspring kidneys. In addition, energy metabolism in fetal and offspring period with green tea extract administration might be related to enzymes which modify epigenetic marks such as DNA methyltransferase 1 and 3a.
Sun, Yongkun; Mukai, Yuuka; Tanaka, Masato; Saito, Takeshi; Sato, Shin; Kurasaki, Masaaki
Effect of Transverse Aortic Constriction on Cardiac Structure, Function and Gene Expression in Pregnant Rats
Background There is an increased risk of heart failure and pulmonary edema in pregnancies complicated by hypertensive disorders. However, in a previous study we found that pregnancy protects against fibrosis and preserves angiogenesis in a rat model of angiotensin II induced cardiac hypertrophy. In this study we test the hypothesis that pregnancy protects against negative effects of increased afterload. Methods Pregnant (gestational day 5.5–8.5) and non-pregnant Wistar rats were randomized to transverse aortic constriction (TAC) or sham surgery. After 14.2±0.14 days echocardiography was performed. Aortic blood pressure and left ventricular (LV) pressure-volume loops were obtained using a conductance catheter. LV collagen content and cardiomyocyte circumference were measured. Myocardial gene expression was assessed by real-time polymerase chain reaction. Results Heart weight was increased by TAC (p<0.001) but not by pregnancy. Cardiac myocyte circumference was larger in pregnant compared to non-pregnant rats independent of TAC (p?=?0.01), however TAC per se did not affect this parameter. Collagen content in LV myocardium was not affected by pregnancy or TAC. TAC increased stroke work more in pregnant rats (34.1±2.4 vs 17.5±2.4 mmHg/mL, p<0.001) than in non-pregnant (28.2±1.7 vs 20.9±1.5 mmHg/mL, p?=?0.06). However, it did not lead to overt heart failure in any group. In pregnant rats, ?-MHC gene expression was reduced by TAC. Increased in the expression of ?-MHC gene was higher in pregnant (5-fold) compared to non-pregnant rats (2-fold) after TAC (p?=?0.001). Nine out of the 19 genes related to cardiac remodeling were affected by pregnancy independent of TAC. Conclusions This study did not support the hypothesis that pregnancy is cardioprotective against the negative effects of increased afterload. Some differences in cardiac structure, function and gene expression between pregnant and non-pregnant rats following TAC indicated that afterload increase is less tolerated in pregnancy.
Songstad, Nils Thomas; Johansen, David; How, Ole-Jacob; Kaaresen, Per Ivar; Ytrehus, Kirsti; Acharya, Ganesh
Protective effects of Allium sativum against defects of hypercholesterolemia on pregnant rats and their offspring
Sixty fertile female and male albino rats of Wistar strain (I male/ 3 females) were used in the present study. The females were divided into four groups of ten rats each. Group 1 received water and standard feeds for thirty-four days. Group 2 was fed with a cholesterol-containing diet (1%) for two weeks prior to onset of gestation and maintained administration till parturition, produce atherosclerosis (34 days). Group 3 received intragastric administration of 100mg homogenate of garlic (Allium sativum)/kg body weight for three weeks prior to onset of gestation as well as throughout the gestation period. Group 4 intragastrically administered garlic for one week of group B and maintained with combined garlic-treatment for the mentioned period. At parturition, the pregnant were sacrificed and serum total cholesterol (TCL), triglycerides (TG), HDL, LDL and creatine kinase activity (CK) were determined. The total numbers of offspring were recorded and examined morphological for congenital abnormalities. Biopsies of heart and dorsal aorta of both pregnant and their offspring (1 day-age) were processed for investigation at light and transmission electron microscopy. The skeleton of the newborn of different experimental groups were stained with alizarin red s and mor-phometric assessment of mandibular and appendicular bone length. The study revealed that the myocardium of atherosclerotic mother exhibited leuhkocytic inflammatory cell infiltration associated with necrosis, eosinophilia of myocardiai fibers, and edema of blood vessels. Ultrastructural studies revealed swelling of mitochondria, disruption of cristae in the myocardiai muscle fibers. The dorsal aorta possessed accumulation of extra-cellular lipid in intima lining of endothelium. The collagenous fibrils in the tunica adventitia became fragile and loosely separated from each other. Numerous foamy lipid loaden cells were detected within the tunica intima causing deterioration of the elastic fibers, resulting in fibrinoid necrosis. Oral supplementation with Allium sativum (100 mg/ kg) ameliorated these effects in myocardium muscle of mothers and offspring; however the dorsal aorta of mothers showed partial amelioration. Hypercholesterolemic mothers exhibited marked alterations in serum TCL, TG, LDL and CK activity. Supplementation with Allium sativum ameliorated the drastic biochemical alterations. Concerning pregnancy, hypercholesterolemia increased the incidence of abortion and abnormalities of the newborn including decreased body weight, reduced ossification of axial (mandible) and appendicular bones. All these effects were markedly ameliorated by supplementation with Allium sativum. The author finally concluded that hypercholesterolemia exhibits pathological alterations of myocardiai muscles reducing its optimal capacity for pumping blood to different body organs along with atherosclerosis of dorsal aorta which intern affect the progress of gestation and development of both morphological and skeletal abnormalities. Allium sativum-supplementation leads to amelioration of both mother and their offspring investigated parameters as a result of its antioxidant activity.
El-Sayyad, Hassan I; Abou-El-Naga, Amoura M; Gadallah, Abdelalim A; Bakr, Iman H
Does l-arginine availability during the early pregnancy alters the immune response of Trypanosoma cruzi infected and pregnant Wistar rats?
Chagas disease induces a strong immune response and l-arginine is an essential amino acid which plays an important role in homeostasis of the immune system. The aims of this study were to evaluate parasitemia, corticosterone levels, production of nitric oxide (NO), fetal morphological measurements, and histology of heart and placenta. Twenty pregnant Wistar rats (180-220g) were grouped in: pregnant control (PC), pregnant control and l-arginine supplied (PCA), pregnant infected (PI), pregnant infected and l-arginine supplied (PIA). Females were infected with 1×10(5) trypomastigotes of the Y strain (3rd day of pregnancy). Animals were supplied with 21mg of l-arginine/kg/day during 14days. PIA showed significant decreased levels of corticosterone and parasitemia. For control groups, any alteration in NO production was found with l-arginine supplementation; for PIA, enhanced nitrite concentrations were observed as compared to PI. Weights and lengths of fetuses were higher in l-arginine treated and infected pregnant rats as compared to untreated ones. Placental weight from the PIA group was significantly increased when compared to PI. In l-arginine treated animals, cardiac tissue showed reduced amastigote burdens. PIA and PI displayed similar placental parasitism. Based on these results, l-arginine supplementation may be potentially useful for the protection against Trypanosoma cruzi during pregnancy. PMID:24786713
da Costa, Cássia Mariana Bronzon; de Freitas, Murilo Rodrigues Barbosa; Brazăo, Vânia; Dos Santos, Carla Domingues; Sala, Miguel Angel; do Prado Júnior, José Clovis; Abrahăo, Ana Amélia Carraro
Thermal physiology of pregnant and lactating female and male long-eared bats, Nyctophilus geoffroyi and N. gouldi
During roosting in summer, reproductive female bats appear to use torpor less frequently and at higher body temperatures (T\\u000a b) than male bats, ostensibly to maximise offspring growth. To test whether field observations result from differences in thermal\\u000a physiology or behavioural thermoregulation during roosting, we measured the thermoregulatory response and energetics of captive\\u000a pregnant and lactating female and male long-eared
Christopher Turbill; Fritz Geiser
Coronary Flow Reserve in Pregnant Rats with Increased Left Ventricular Afterload
Background Coronary flow reserve (CFR) is used as a measure of coronary endothelial function. We investigated the effect of increased afterload on CFR of pregnant and non-pregnant rats. Methods Afterload increase in Wister rats (both pregnant and non-pregnant) was achieved by the infusion of angiotensin II (Ang II) for ?10 days or by subjecting them to transverse aortic constriction (TAC) for ?14 days. Control groups were infused with 0.9% NaCl or had sham surgery, respectively. In pregnant rats, the experiments were performed close to term gestation. Doppler velocity waveforms of the left main coronary artery were recorded using a high resolution ultrasound imaging system (Vevo 770, VisualSonics, Canada) at baseline while the animals were anesthetized with 1.5% inhaled isoflurane, and during maximal coronary dilatation obtained by the inhalation of 3.5% of isoflurane. CFR was calculated as the ratio between the peak coronary flow velocities (CFRpeak) and the velocity-time integrals (CFRVTI) recorded at hyperemia and at baseline. Results CFR could be calculated in 60 of 75 (80%) animals. There were no differences in CFR between intervention and control groups irrespective of whether afterload was increased by Ang II or TAC. In the TAC-study CFRpeak (1.54±0.07 vs 1.85±0.17; p?=?0.03) was decreased in pregnant compared to non-pregnant shams. When sham animals from both studies were pooled together both CFRpeak (1.42±0.07 vs 1.86±0.16; p?=?0.005) as well as CFRVTI (1.45±0.07 vs 1.78±0.12; p?=?0.03) were significantly lower in pregnant rats compared to non-pregnant. Conclusions CFR can be measured non-invasively in rats using Doppler echocardiography and high concentrations of inhaled isoflurane as a coronary vasodilator. In pregnant rats, CFR is reduced close to term. CFR is not affected by increased left ventricular afterload caused by chronic Ang II infusion or TAC.
Songstad, Nils Thomas; Serrano, Maria C.; Sitras, Vasilis; Johansen, Davis; Ytrehus, Kirsti; Acharya, Ganesh
Ameloblastoma in a female Wistar rat.
A spontaneous ameloblastoma of the right mandible is described in a 120-week-old female Wistar rat (strain Chbb: THOM). The tumour had a locally aggressive growth pattern and was histologically characterized by sheets and islands of odontogenic epithelium bounded by a palisaded layer of ameloblast-like cells. Because of multifocal keratinizing squamous metaplasia of the stellate reticulum tissue, the tumour was classified as an acanthomatous ameloblastoma. Cyst formation, areas of stromal hyalinization and enamel matrix-like inclusions were further characteristics of the neoplasm. The epithelial elements stained strongly positive for broad spectrum cytokeratins. PMID:8871064
Ernst, H; Mirea, D
Phasic Oscillations of Extracellular Potassium (Ko) in Pregnant Rat Myometrium
K-sensitive microelectrodes were used to measure K+ within the extracellular space (Ko) of pregnant rat myometrium. Contractile activity was monitored by measuring either force or bioelectrical signals. Single and double-barreled electrodes were used. Double-barreled electrodes allowed monitoring of electrical activity 15 microns from the site of Ko measurement. From double-barreled electrode experiments, the bioelectrical burst started first, and then Ko began to rise 0.6 ± 0.1 seconds later. This delay indicates that K+ leaves the cells in response to local electrical activity rather than vice versa. Four control experiments were performed to assess the influence of electrical artifacts caused by tissue motion on Ko values. When observed, artifacts were negative and transient, and hence would result in an underestimation of Ko rises. Artifacts were minimized when tissue motion was minimized by fixing the tissue at both ends. At 37°C, 7 single barreled experiments and 45 contractions were analyzed. Resting Ko was within 1 mM of bath K+ (5 mM) at the beginning and end of the experiments. Ko rose during the contraction, fell after the completion of the contraction, and normalized before the next contraction began. Peak Ko values observed during force production were 18.8 ± 5.9 mM, a value high enough to modulate tissue-level electrical activity. Ko required 15.7 ± 2.8 seconds to normalize halfway (t50). Six experiments expressing 38 contractions were performed at 24°C. The contraction period was longer at 24°C. Values for peak Ko (26.2 ± 9.9 mM) and t50 (29.8±16.2 sec) were both larger than at 37°C (p<0.0003 for both). The direct relationships between peak Ko, t50 and the contraction period, suggest elevations in Ko may modulate contraction frequency. The myometrial interstitial space appears to be functionally important, and Ko metabolism may participate in cell-cell interactions.
Young, Roger C.; Goloman, Gabriela
Short and long effects of Citrullus colocynthis L. on reproductive system and fertility in female Spague-Dawley rats.
Aim of this study is to investigate the toxic effects of Citrullus colocynthis L. (400 mg/kg/body wight) on the reproductive system after administration to female Sprague-Dawley rats weighting 250-300 g for two time periods 4 and 12 weeks. Twenty adult female rats were divided into two groups and Citrullus colocynthis L. were intraperitoneally injected to experimental animals in dose of 400 mg/kg/body wight. First group containing 10 rats received treatment for 4 weeks and a second group of 10 rats received the same dose of treatment for a period of 12 weeks and compared with twenty non-exposed female rats received vehicle treatment. Female rats were allowed mating with males after 10 days prior to the last administration dose. Animals were autopsied under light anesthesia after mating and several parameters were determined including: number of pregnant rats, body and reproductive organ weight, number of implantation sites, viable fetuses and resorption sites. Assessment of pregnancies in females was measured and the significance of these results was calculated using students t and Chi-square tests. The effect of Citrullus colocynthis L. exposure on fertility was assessed in terms of pregnant rats number, implantation sites, viable fetuses and resorption sites. Exposure to Citrullus colocynthis L. for 4 weeks did not have much effect on fertility. Significant decrease in the relative ovarian weights and embryo weights in rats exposed to Citrullus colocynthis L. were observed. Exposure to Citrullus colocynthis L. for a 12 weeks resulted in a reduction in the percentage of pregnancies and in the number of implantation sites when compared with controls in both treatment periods. Rats receiving 12 weeks treatment showed a decrease in ovarian weights and a decrease in viable fetus's number. These results indicate that long-term exposure of female rats to Citrullus colocynthis L. causes adverse effects on the reproductive system and fertility. PMID:19070085
Qazan, Walid Sh; Almasad, Motasem M; Daradka, Haytham
Effects of low doses of alcohol on delta-9-tetrahydrocannabinol's effects in pregnant rats
Pregnant rats were intubated with 50 mg/kg of delta-9-tetrahydrocannabinol (THC) or with THC plus alcohol to determine if a low dose of alcohol would significantly increase blood levels of THC. On the basis of this study, a second study was conducted in which pregnant rats were intubated with THC plus alcohol from gestation day six to parturition. THC reduced birth weights but did not significantly affect litter size or passive avoidance learning. Alcohol did not have a significant effect on offspring birth weight nor did it interact with THC to affect offspring.
Abel, E.L.; Subramanian, M.G. (Wayne State Univ., Detroit, MI (USA))
The hypothesis that hepatic metallothionein (MT) induction in the pregnant animal results in a Zn deficiency in the embryo was tested by treating pregnant rats with a-hederin, reported to induce MT in rat liver. orphological development was assessed in term fetuses. ingle dose of...
Disposition of Orally Administered 2,2Bis(4-hydroxyphenyl)propane (Bisphenol A) in Pregnant Rats and the Placental Transfer to Fetuses
We studied the disposition of bisphenol A (BPA) in pregnant female F344\\/DuCrj(Fischer) rats and its placental transfer to fetuses after a single oral administration of 1 g\\/kg BPA dissolved in propylene glycol. BPA in maternal blood, liver, and kidney reached maximal concentrations (14.7, 171, and 36µg\\/g) 20 min after the administration and gradually decreased. The levels were 2-5% of the
Osamu Takahashi; Shinshi Oishi
Oxytocin regulates the expression of aquaporin 5 in the late-pregnant rat uterus.
Aquaporins (AQPs) are integral membrane channels responsible for the transport of water across a cell membrane. Based on reports that AQPs are present and accumulate in the female reproductive tract late in pregnancy, our aim was to study the expression of AQP isoforms (AQP1, 2, 3, 5, 8, and 9) at the end of pregnancy in rat in order to determine if they play a role in parturition. Reverse-transcriptase PCR revealed that specific Aqp mRNAs were detectable in the myometrium of non-pregnant and late-pregnancy (Days 18, 20, 21, and 22 of pregnancy) rat uteri. The expression of Aqp5 mRNA and protein were most pronounced on Days 18-21, and were dramatically decreased on Day 22 of pregnancy. In contrast, a significant increase was found in the level of Aqp5 transcript in whole-blood samples on the last day of pregnancy. The effect of oxytocin on myometrial Aqp5 expression in an organ bath was also investigated. The level of Aqp5 mRNA significantly decreased 5?min after oxytocin (10(-8) ?M) administration, similarly to its profile on the day of delivery; this effect was sensitive to the oxytocin antagonist atosiban. The vasopressin analog desmopressin (3.7?×?10(-8) ?M), on the other hand, did not alter the expression of Aqp5, but did increased the amount of Aqp2 mRNA, an effect that was atosiban-resistant. These results lead us to propose that oxytocin selectively influences the expression of Aqp5 at the end of pregnancy, and may participate in events that lead to parturition in the rat. The sudden increase of AQP5 in the blood on the last day of pregnancy may serve as a marker that indicates the initiation of delivery. Mol. Reprod. Dev. 81: 524-530, 2014. © 2014 Wiley Periodicals, Inc. PMID:24644013
Ducza, Eszter; Seres, Adrienn B; Hajagos-Tóth, Judit; Falkay, George; Gáspár, Róbert
Metal concentrations in blood and hair in pregnant females in southern Sweden.
The study described here was comprised of 100 pregnant females from two prenatal care units at the cities of Hassleholm and Simrishamn in southern Sweden. It included a questionnaire as well as whole blood (total mercury, cadmium, and lead) and hair (total mercury) sampling (collection period 2002-2003). The median values of total mercury (B-Hg 0.70 microg/L; range 0.27-2.1 microg/L), cadmium (0.30 microg/L, 0.05-4.8 microg/L) and lead (11.0 microg/L, 4.2-79 microg/L) in whole blood were low in the total material, as were the hair mercury concentrations (Hair-Hg 0.22 microg/g, 0.04-0.83 microg/g). In a multiple linear regression model, B-Hg was related to the number of fish meals per week and to the number of occlusal amalgam fillings (multiple r = 0.51; p < .001). The levels of mercury, cadmium, and lead in whole blood were lower than suggested biological reference intervals, and did not indicate risks for adverse health effects. PMID:20104833
Gerhardsson, Lars; Lundh, Thomas
Reversal of prenatal morphine exposure-induced memory deficit in male but not female rats.
Impaired memory performance in offspring is one of the long-lasting neurobehavioral consequences of prenatal opiate exposure. Here, we studied the effects of prenatal morphine exposure on inhibitory avoidance memory performance in male and female offspring and also investigated whether these deficits are reversible during the postnatal development. Pregnant Wistar rats received morphine sulfate through drinking water, from the first day of gestation up to the day 13, M????, or to the time of delivery, M????. Four- and ten-week-old (adolescent and adult, respectively) male and female offspring were subjected to behavioral assays and then analysis of proteins involved in apoptosis or in synaptic plasticity. Results revealed that adolescent and adult female rats failed in passive avoidance retention task in both M???? and M???? groups. Adolescent and adult male offspring were similar to control animals in M???? group. However M???? impaired retention task in prepubertal male offspring, and this memory loss was repaired in postpubertal stage. Consistently, Bax/Bcl-2 ratio and cleaved caspase-3 were significantly increased in both M???? and M???? adolescent and adult female rats, but only in M???? adolescent male rats. Furthermore, prenatal morphine exposure reduced the expression of brain-derived neurotrophic factor precursor protein in adolescent and adult female offspring and also decreased p-ca(2+)/calmodulin-dependent kinase II/ca(2+)/calmodulin-dependent kinase II ratio in adolescent male and female rats. Altogether, the results show that prenatal morphine exposure, depending on the time or duration of exposure, has distinct effects on male and female rats, and postnatal development may reverse these deficits more likely in males. PMID:22864979
Nasiraei-Moghadam, Shiva; Sherafat, Mohammad Amin; Safari, Mir-Shahram; Moradi, Fatemeh; Ahmadiani, Abolhassan; Dargahi, Leila
Transient prenatal androgen exposure produces metabolic syndrome in adult female rats
Androgen exposure during intrauterine life in nonhuman primates and in sheep results in a phenocopy of the reproductive and metabolic features of polycystic ovary syndrome (PCOS). Such exposure also results in reproductive features of PCOS in rodents. We investigated whether transient prenatal androgen treatment produced metabolic abnormalities in adult female rats and the mechanisms of these changes. Pregnant dams received free testosterone or vehicle injections during late gestation, and their female offspring were fed regular or high-fat diet (HFD). At 60 days of age, prenatally androgenized (PA) rats exhibited significantly increased body weight; parametrial and subcutaneous fat; serum insulin, cholesterol and triglyceride levels; and hepatic triglyceride content (all P < 0.0125). There were no significant differences in insulin sensitivity by intraperitoneal insulin tolerance test or insulin signaling in liver or skeletal muscle. HFD had similar effects to PA on body weight and composition as well as on circulating triglyceride levels. HFD further increased hepatic triglyceride content to a similar extent in both PA and control rats. In PA rats, HFD did not further increase circulating insulin, triglyceride, or cholesterol levels. In control rats, HFD increased insulin levels, but to a lesser extent than PA alone (?2.5- vs. ?12-fold, respectively). We conclude that transient prenatal androgen exposure produces features of the metabolic syndrome in adult female rats. Dyslipidemia and hepatic steatosis appear to be mediated by PA-induced increases in adiposity, whereas hyperinsulinemia appears to be a direct result of PA.
Demissie, Marek; Lazic, Milos; Foecking, Eileen M.; Aird, Fraser; Dunaif, Andrea; Levine, Jon E.
Trichloroacetonitrile (TCAN) is a by-product of the chlorine disinfection of water containing natural organic material. When administered by gavage to pregnant Long-Evans rats in a medium-chain triglyceride vehicle, tricaprylin oil (Tricap), at a volume of 10 ml/kg, TCAN induced ...
EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE PREGNANT F344 RAT. S. R. Bielmeier1, A. S. Murr2, D. S. Best2, J. M. Goldman2, and M. G. Narotsky2 1 Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC, USA 2 Reproductive T...
Serum proteins and enzymes in pregnant rats treated with epoxy resin or triethylenetetraamine stabilizer
A study was made of the serum and amniotic fluid levels of several acute phase reactants (seromucoid, haptoglobin, and sialic acid) and enzymatic activities (lactate dehydrogenase, leucylnaphthylamidase, ?-glutamyltranspeptidase, aminotransferases, cholmesterase, and alkaline and acid phosphatases) in pregnant and nonpregnant rats treated with epoxy resin Epidian 5 or triethylenetetraamine stabilizer. Changes produced by the action of the chemicals were similar, including
W. Dobryszycka; M. Warwas; A. Woytofi; J. Woyto?; J. Szacki
Prolactin Stimulation of Maternal Behavior in Female Rats
Inexperienced, hypophysectomized female rats treated with steroids were used in experiments to investigate the roles of the pituitary gland and prolactin in the expression of maternal behavior. Administration of ovine prolactin or treatment with ectopic pituitary grafts, which release prolactin into the circulation, stimulated maternal care in these females toward rat young. Steroid treatment alone, while stimulating maternal behavior in
Robert S. Bridges; Rosemarie Dibiase; Donna D. Loundes; Paul C. Doherty
In utero and lactational exposure to fenvalerate disrupts reproductive function in female rats.
Fenvalerate is a synthetic pyrethroid insecticide used in agriculture and domestic insect control. Some studies have proposed that it may act as an environmental estrogen; other studies suggest possible genotoxicity in germ cells. This study aimed to evaluate the effects of fenvalerate on the female reproduction in rats whose mothers were exposed during gestation and lactation. Pregnant Wistar rats were exposed to fenvalerate (40 mg/kg) or corn oil (vehicle) orally from gestational day 12 until the end of lactation. The dose selection was based on previous studies, whereas this was considered an effective dose. Results showed decreases in ovarian weight, pre-antral follicles and corpora lutea at PND 75 and an increase in the resorption number, when fertility test was performed at PND 80. Under some experimental conditions, fenvalerate may impair reproductive development of female offspring, manifested as reduced fecundity and ovulation number, resulting from the impairment in corpora lutea counting. PMID:21889588
Guerra, Marina T; de Toledo, Fabíola C; Kempinas, Wilma De G
Phenobarbital pretreatment was found not to induce Triton X-100 activated hepatic microsomal neonatal UDP-glucuronyltransferase activity towards phenolphthalein in male, female and pregnant female rats....
Failure of Phenobarbital to Induce Rat Hepatic Microsomal UDP-Glucuronyltransferase toward Phenolphthalein.
National Technical Information Service (NTIS)
Phenobarbital pretreatment was found not to induce Triton X-100 activated hepatic microsomal neonatal UDP-glucuronyltransferase activity towards phenolphthalein in male, female and pregnant female rats.
K. T. Kitchin
Fetal programming of adult hypertension in female rat offspring exposed to androgens in utero
Aims The influence of prenatal factors on the development of arterial hypertension has gained considerable interest in recent years. We examined the effects of prenatal testosterone treatment on blood pressure in adult female rats. Further, to define the mechanisms whereby blood pressure may be raised, we examined vascular endothelial function and nitric oxide synthesis. Methods and Results Testosterone propionate (0.5mg/kg/day;SC) or vehicle was administered to pregnant Sprague-Dawley rats from gestational day 15–19. Maternal feed intake and plasma levels of steroid hormones were measured in the dams. In the female offspring, birth weight, growth rate, blood pressure, vascular reactivity, eNOS expression, and nitric oxide production were examined. In the pregnant rats, testosterone-treatment increased plasma testosterone levels by 2-fold without any significant changes in 17?-estradiol, progesterone and corticosterone levels. Testosterone-treatment did not affect maternal feed intake. The pups born to testosterone mothers were smaller in size but exhibited catch-up growth. The blood pressure in the testosterone offspring at 6 months of age was significantly higher compared to controls. Endothelium-intact mesenteric arteries from testosterone group exhibited increased contractile responses to phenylephrine, decreased vasodilation to acetylcholine and unaltered responses to sodium nitroprusside in comparison to control rats. Testosterone rats demonstrated decreased expression for eNOS, and reduced nitric oxide production. Conclusions Our data show that elevated plasma maternal testosterone levels: (1) causes low birth weight followed by catch-up growth and hypertension in female offspring; (2) alters endothelium-dependent vascular responses. The endothelial dysfunction is associated with decreased activity/expression of eNOS.
Sathishkumar, K.; Elkins, Rebekah; Yallampalli, Uma; Balakrishnan, Meena; Yallampalli, Chandrasekhar
Investigation on the role of Spirulina platensis in ameliorating behavioural changes, thyroid dysfunction and oxidative stress in offspring of pregnant rats exposed to fluoride.
The study investigated the role of Spirulina platensis in reversing sodium fluoride-induced thyroid, neurodevelopment and oxidative alterations in offspring of pregnant rats. The total antioxidant activity, phycocyanins, and ? carotene content were quantified in Spirulina. Thirty female pregnant rats were allocated to six groups and treatment initiated orally from embryonic day (ED) 6 to postnatal day (PND) 15. Treatment groups included control, Spirulina alone, sodium fluoride (20 mg/kg) alone, and sodium fluoride along with Spirulina (250 and 500 mg/kg). Serum fluoride levels were determined on ED 20 and PND 11. Offspring were subjected to behavioural testing, estimation of thyroid levels, oxidative measurements in brain mitochondrial fraction and histological evaluation of the cerebellum. Fluoride-induced alterations in thyroid hormones, behaviour and increased oxidative stress. Spirulina augmented the displacement of fluoride, facilitated antioxidant formation, improved behaviour and protected Purkinje cells. Supplementing Spirulina during pregnancy could reduce the risk of fluoride toxicity in offspring. PMID:23578649
Banji, David; Banji, Otilia J F; Pratusha, N Gouri; Annamalai, A R
Toxicokinetic aspects of thiocyanate after oral exposure to cyanide in female Wistar rats in different physiological states.
Cyanide (CN) is an ion that has been well studied in toxicology and has been associated with several intoxication episodes: the ingestion of contaminated foods and water, chemical war, suicides, homicides, occupational exposures and the use of certain medicines. The aim of the present study was to determine the toxicokinetic parameters of thiocyante (SCN), the main metabolite of CN, after oral administration of potassium cyanide (KCN) to female rats at diestrus, gestational and lactational periods. Female Wistar rats were divided into three equal groups: virgins in the diestrus phase of the estrus cycle, females at the 14th day of gestation and females at the 14th day of lactation. Each group of rats received 3.0?mg of potassium cyanide per kilogram (KCN/kg body weight) by gavage, and blood was collected at several time points. We also collected amniotic fluid from pregnant rats and milk from the nursing rats to analyze thiocyanate concentration. The results showed that SCN levels were significantly increased in serum, milk and amniotic fluid after administration of KCN. In conclusion, the results of the present study evidence that the metabolism of CN varies greatly considering the physiologic state of the female rat, being females at estrus probably more exposed by these substances than at gestation and lactation because in these states there are other compartments, fetus and milk, which may capture these substances, as demonstrated by the V(d) values. PMID:23841473
de Sousa, Altamir Benedito; Górniak, Silvana Lima
[Comparative analysis of cerebral blood flow autoregulation in pregnant and nonpregnant rats].
It is known, that disturbances in functioning of cerebral blood flow autoregulation during pregnancy may cause severe neurological complications in case of hypertensive episodes. The aim of this study was comparison of autoregulatory responses of cerebral blood flow in pregnant and nonpregnant rats and analysis of their possible mechanisms. Experiments were carried out on two groups of nonpregnant white rats, and two groups of late-pregnant. All test on autoregulation of cerebral blood flow were provided in conditions of acute experiment under chloral hydrate anesthesia. Gradual changes in systemic arterial pressure were caused by occlusion of abdominal aorta by means of catheter with inflatable tip. The local cerebral blood flow was registered using Hydrogen Clearance technique. Before beginning of autoregulatory tests two groups of animals were treated with nitric oxide synthase inhibitor L-NAME. It was established that in late-pregnancy the cerebral blood flow autoregulatory curve in comparison with nonpregnant animals is shifted to the low levels of systemic arterial pressure. Inhibition of nitric oxide synthase by L-NAME caused the shift of autoregulatory curve to the high levels of systemic arterial pressure in both nonpregnant and pregnant animals. Besides, the differences in autoregulatory responses between nonpregnant and pregnant animals taking place in untreated by L-NAME groups were completely eliminated. These finding allow concluding that in late-pregnancy the shift of cerebral blood flow autoregulatory curve to low levels of systemic arterial pressure is caused by increased production of nitric oxide. PMID:19202232
Dzhanelidze, M A
The effects of pregnancy, lactation, and primiparity on object-in-place memory of female rats.
Maternal physiology and behavior change dramatically over the course of pregnancy to nurture the fetus and prepare for motherhood. Further, the experience of motherhood itself continues to influence brain functioning well after birth, shaping behavior to promote the survival of offspring. To meet these goals, cognitive abilities, such as spatial memory and navigation, may be enhanced to facilitate foraging behavior. Existing studies on pregnant and maternal rats demonstrate enhanced cognitive function in specific spatial domains. We adopted a novel object-in-place task to assess the ability of female rats to integrate information about specific objects in specific locations, a critical element of foraging behavior. Using a longitudinal design to study changes in spatial memory across pregnancy and motherhood, an advantage in the object-in-place memory of primiparous female rats compared to nulliparous females emerged during lactation not during pregnancy, and was maintained after weaning at 42 days postpartum. This enhancement was not dependent on the non-mnemonic variables of anxiety or neophobia. Parity did not affect the type of learning strategy used by females to locate a cued escape platform on a dual-solution water maze task. Results indicate that the enhancement of object-in-place memory, a cognitive function that facilitates foraging, emerged after pregnancy during the postpartum period of lactation and persisted for several weeks after weaning of offspring. PMID:24211441
Cost, Katherine Tombeau; Lobell, Thomas D; Williams-Yee, Zari N; Henderson, Sherryl; Dohanich, Gary
Hypertension in Response to Chronic Reductions in Uterine Perfusion in Pregnant Rats
Reductions in uterine perfusion pressure (RUPP) in pregnant rats is associated with increased tumor necrosis factor-? (TNF-?). This study was designed to determine the role of endogenous TNF-? in mediating changes in arterial pressure and endothelin-1 (ET-1) in RUPP rats. To achieve this goal we examined the effect of RUPP in the presence and absence of a TNF-?–soluble receptor, etanerecept (0.4 mg/kg). Mean arterial pressure increased from 102±1 mm Hg in normal pregnant (NP) rats to 134±3 mmHg (P<0.05) in RUPP rats. Serum TNF-? increased to 40±7.6 pg/mL in RUPP rats (n=24) versus 14.8±3.3 pg/mL (n=16; P<0.05) in NP rats. Administration of etanerecept decreased TNF-? in RUPP rats (n=20) to 17.2±3 pg/mL and mean arterial pressure to 118±2 mmHg (P<0.05). Tissue ET-1 decreased in etanerecept-treated RUPP rats compared with control RUPP rats. The direct effect of TNF-? blockade on endothelial activation in response to placental ischemia was examined in human umbilical vein endothelial cells. ET-1 secreted from human umbilical vein endothelial cells treated with RUPP serum was 59.2±16 pg/mg and decreased when etanerecept was added to the medium with RUPP serum (7.60±0.77 pg/mg), as well as in response to serum from etanerecept-treated RUPP rats (7.30±0.55 pg/mg; P<0.001). ET-1 secreted from human umbilical vein endothelial cells was 15.6±2 pg/mg when treated with NP serum. These data support the hypothesis that endogenous TNF-? is an important stimulus for ET-1 in response to placental ischemia and is important in mediating endothelial cell activation and hypertension during pregnancy.
LaMarca, Babbette; Speed, Josh; Fournier, Lillian; Babcock, Sara A.; Berry, Hunter; Cockrell, Kathy; Granger, Joey P.
This study describes the maternal-fetal disposition of bisphenol A and its distribution into the placenta and amniotic fluid after iv injection (2 mg\\/kg) to pregnant Sprague-Dawley rats. Bisphenol A was distributed extensively to the placenta and fetus, with their respective AUC values 4.4- and 2.2-fold greater than AUC for the maternal serum. In contrast, the distribution of bisphenol A into
Beom Soo Shin; Sun Dong Yoo; Chang Youn Cho; Ji Hoon Jung; Byung Mu Lee; Jung Ha Kim; Kang Choon Lee; Soon-Young Han; Hyung Sik Kim; Kui Lea Park
Effects of experimental diabetes on the vitamin D metabolism of pregnant rats and their fetuses
Summary The effects of streptozotocin-induced diabetes on the vitamin D metabolism of pregnant rats were investigated in mothers and\\u000a their fetuses, 11 and 14 days after streptozotocin (SZ) injection, i.e., on days 18 and 21 of gestation. In the mothers' plasma,\\u000a the levels of 25-hydroxycholecalciferol (25OHD) and 1,25-dihydroxycholecalciferol (1,25(OH)2 D) were not different from control levels on day 18, but on
J. Demignon; C. Rebut-Bonneton
Enhancement of gentamicin-induced nephrotoxicity by Mg deficiency in non-pregnant rats
Non-pregnant rats fed an Mg-deficient diet showed some degenerated and calcified proximal tubules in the inner region of the medullary rays accompanied by reduced or absent enzyme activities. After gentamicin treatment some damaged convoluted proximal tubules occurred. Enzyme histochemistry revealed decreased activities for brush border and lysosomal hydrolases; using immunohis-tochemistry lesions were detectable for the cytoskeletal proteins keratin and vimentin.
R. Gossrau; T. Giinthcr; R. Graf
Effects of IFN-? on IL-18 Expression in Pregnant Rats and Pregnancy Outcomes
The present study focused on establishing the effects of interferon-gamma (IFN-?) on interleukin-18 (IL-18) expression patterns and pregnancy outcomes in pregnant rats. Pregnant rats at the post-implantation stage were randomized into control, low IFN-? (L-IFN-?) and high IFN-? groups (H-IFN-?) that received normal saline, 100 IU/g of IFN-? and 500 IU/g of IFN-? vaginal muscular injection, respectively. The effects of IFN-? on IL-18 expression and pregnancy outcomes were assessed systematically using several methods, including immunohistochemistry streptavidin-perosidase (SP), image pattern analysis, enzyme-linked immune-sorbent assay (ELISA), whole blood count (WBC) count, microscopy and visual observation. IL-18 was detected in the uteri of all pregnant rats, and mainly distributed in the endometrium, decidual cells, vascular endothelium and myometrium. Immunohistochemistry and image pattern analyses revealed significantly lower IL-18 expression in the H-IFN-? group compared to the L-IFN-? and control groups (p<0.01), indicating that high doses of IFN-? induce downregulation of IL-18 in the uterus of pregnant rats. ELISA results disclosed that IL-18 expression in peripheral blood of the H-IFN-? group was lower than that of the L-IFN-? group (p<0.05), and significantly reduced compared to the control group (p<0.01). Moreover, the number of peripheral leukocytes in the H-IFN-? group was significantly higher than those in the control and L-IFN-? groups (p<0.01). Morphology analysis showed no evident differences between the L-IFN-? and control groups. However, for the H-IFN-? group, uterine mucosa bleeding, necrosis and excoriation were observed using microscopy. Visual observation revealed marroon, swelling, crassitude and no embryo in the uterus, which are obvious indicators of abortion. These results indicate that IFN-? plays a regulatory role in IL-18 expression in the uterus and peripheral blood of pregnant rats at the post-implantation stage. Moreover, high levels (500 IU/g) of IFN-? influence normal pregnancy at the early stages in rats by downregulating IL-18 expression in the uterus and peripheral blood and increasing the number of peripheral leukocytes, consequently triggering termination of pregnancy.
Si, Li-fang; Zhang, Shou-Yan; Gao, Chun-sheng; Chen, Shu-lin; Zhao, Jin; Cheng, Xiang-chao
Exercise-training reduced blood pressure and improve placental vascularization in pregnant spontaneously hypertensive rats--pilot study.
Assess the effects of exercise-training on resting arterial pressure and heart rate, placental fetuses morphologic alterations in pregnant spontaneously hypertensive rats (SHRs).Twenty SHRs and their respective control normotensive rats (WKY) were submitted or not to a swimming protocol during 9 weeks, resulting in four pregnant experimental groups: sedentary hypertensive (PSH), trained hypertensive (PTH), sedentary normotensive (PSN), and trained normotensive (PTN). Exercise-training by swimming attenuates arterial pressure in pregnant SHRs, and can contribute to an increase in the length of fetuses and the percentage of the vessels in the placenta. PMID:22506932
Abate, Débora Tavares de Resende e Silva; Barbosa Neto, Octavio; Rossi e Silva, Renata Calciolari; Faleiros, Ana Carolina Guimarăes; Correa, Rosana Rosa Miranda; da Silva, Valdo José Dias; Castro, Eumęnia Costa da Cunha; Reis, Marlene Antônia
Neonatal handling and reproductive function in female rats
Neonatal handling induces anovulatory estrous cycles and decreases sexual receptivity in female rats. The synchro- nous secretion of hormones from the gonads (estradiol (E2) and progesterone (P)), pituitary (luteinizing (LH) and follicle-stimulating (FSH) hormones) and hypothalamus (LH-releasing hormone (LHRH)) are essential for the reproductive functions in female rats. The present study aimed to describe the plasma levels of E2 and
C M Gomes; P Ramos de Paula; G S Severino; C V V Helena; J A Anselmo-Franci; C R Franci; G L Sanvitto; A B Lucion
High alcohol intake in female Sardinian alcohol-preferring rats.
Sardinian alcohol-preferring (sP) rats have been selectively bred for high alcohol preference and consumption. When exposed to the standard, home cage 2-bottle "alcohol (10%, v/v) vs. water" choice regimen with continuous access, male sP rats consume daily approximately 6 g/kg alcohol. Conversely, when exposed to the intermittent (once every other day) access to 2 bottles containing alcohol (20%, v/v) and water, respectively, male sP rats display marked increases in daily alcohol intake and signs of alcohol intoxication and "behavioral" dependence. The present study was designed to assess alcohol intake in female sP rats exposed, under the 2-bottle choice regimen, to (a) 10% (v/v) alcohol with continuous access (CA10%), (b) 10% (v/v) alcohol with intermittent access (IA10%), (c) 20% (v/v) alcohol with continuous access (CA20%), and (d) 20% (v/v) alcohol with intermittent access (IA20%). Male sP rats (exposed to CA10% and IA20% conditions) were included for comparison. Over 20 daily drinking sessions, daily alcohol intake in female CA10% and IA20% rats averaged 7.0 and 9.6 g/kg, respectively. The rank of alcohol intake was IA20% > IA10% = CA20% > CA10%. Conversely, daily alcohol intake in male CA10% and IA20% rats averaged 6.0 and 8.2 g/kg, respectively. Comparison of female and male rats yielded the following rank of alcohol intake: female IA20% > male IA20% > female CA10% ? male CA10%. An additional experiment found that alcohol drinking during the first hour of the drinking session produced mean blood alcohol levels of 35-40 mg% and 85-100 mg% in the CA10% and IA20% rats, respectively. These results (a) extend to female sP rats previous data demonstrating the capacity of the IA20% condition to markedly escalate alcohol drinking, and (b) demonstrate that female sP rats consume more alcohol than male sP rats. This sex difference is more evident under the IA20% condition, suggesting that female sP rats are highly sensitive to the promoting effect of the IA20% condition on alcohol drinking. These data contribute to the characterization of sP rats as a model of excessive alcohol consumption. PMID:24555906
Loi, Barbara; Colombo, Giancarlo; Maccioni, Paola; Carai, Mauro A M; Franconi, Flavia; Gessa, Gian Luigi
Conditioned mate-guarding behavior in the female rat.
Female and male rats are often described as having a promiscuous mating strategy, yet simple Pavlovian conditioning paradigms, in which a neutral odor or strain-related cues are paired with preferred sexual reward states during an animal's first sexual experiences, shift this strategy toward copulatory and mate preferences for partners bearing the familiar odor or strain cue. We examined whether female rats given exclusive rewarding copulation with one particular male would display mate-guarding behavior, a strong index of monogamous mating. Ovariectomized, hormone-primed female Long-Evans rats were given their first 10 paced sexual experiences at 4-day intervals with a particular unscented male of the same strain. A final test was conducted in an open field 4-days later in which the primed, partnered female was given access to the male partner and a fully-primed competitor female. In this situation, the partnered females mounted the competitor female repeatedly if she came near the vicinity of the male. This behavior prevented the male from copulating with the competitor, and was not displayed if partnered females could not pace the rate of copulatory behavior efficiently during the training trials, nor was it displayed by the competitor females. Fos expression was examined in both the partnered and competitor females after the final open field test. Partnered females had significantly higher expression within the supraoptic nucleus and nucleus accumbens shell compared to partnered females that did not develop this behavior or competitor females. These data show that females engaged in paced copulation with the same male display mate-guarding when exposed to that male and a competitor female. Increased activation of the SON and NAc may underlie this behavior. PMID:24768651
Holley, Amanda; Shalev, Shy; Bellevue, Shannon; Pfaus, James G
Fluid and Electrolyte Content in Pregnant Rats and Their Offspring Following Flight Aboard Cosmos-1514 Biosatellite.
National Technical Information Service (NTIS)
Female rats were flown on Cosmos 1514 for five days during gestation days 13 through 18. The rats showed a significant reduction of the Ca concentration in the liver and kidneys, a smaller decrease in the skin, and no changes in bones. The weight of the f...
Y. I. Shakhmatova Y. A. Lavrova Y. V. Natochin L. V. Serova L. A. Denisova
Effect of propranolol treatment in pregnant rats on motor activity and avoidance learning of the offspring
Rats born to mothers treated with propranolol, during days 8–22 of gestation, displayed hyperactivity in the open field which lasted up to 60 days of age and an impairment of avoidance in the shuttle box which was more marked in the male rats. Females exhibited hyperactivity in the open field but developed impaired avoidance learning only when exposed prenatally to
Z. Speiser; A. Shved; S. Gitter
Prenatal androgen excess enhances stimulation of the GNRH pulse in pubertal female rats.
In adolescent girls with polycystic ovary syndrome (PCOS), neuroendocrine derangements manifest after the onset of puberty, characterized by rapid LH pulse frequency. The early mechanism underlying the pubertal regulation of the GNRH/LH pulsatile release in adolescents with PCOS remains uncertain. To determine the effects of prenatal androgen exposure on the activation of GNRH neurons and generation of LH pulse at puberty, we administrated 5?-dihydrotestosterone to pregnant rats and observed serum LH levels and expression of hypothalamic genes in female offspring from postnatal 4 to 8 weeks. The 6-week-old prenatally androgenized (PNA) female rats exhibited an increase in LH pulse frequency. The hypothalamic expression of neurokinin B (Nkb (Tac2)) and Lepr mRNA levels in PNA rats increased remarkably before puberty and remained high during puberty, whereas elevated Kiss1 mRNA levels were detected only after the onset of puberty. Exogenous kisspeptin, NK3R agonist, and leptin triggered tonic stimulation of GNRH neurons and increased LH secretion in 6-week-old PNA rats. Leptin upregulated Kiss1 mRNA levels in the hypothalamus of pubertal PNA rats; however, pretreatment with a kisspeptin antagonist failed to suppress the elevated serum LH stimulated by leptin, indicating that the stimulatory effects of leptin may be conveyed indirectly to GNRH neurons via other neural components within the GNRH neuronal network, rather than through the kisspeptin-GPR54 pathway. These findings validate the hypotheses that NKB and leptin play an essential role in the activation of GNRH neurons and initiation of increased LH pulse frequency in PNA female rats at puberty and that kisspeptin may coordinate their stimulatory effects on LH release. PMID:24829217
Yan, Xiaonan; Yuan, Chun; Zhao, Nannan; Cui, Yugui; Liu, Jiayin
Influence of estrogen in the acquisition of intravenously self-administered heroin in female rats
Previous research indicates that female rats acquire cocaine and heroin self-administration at a faster rate than male rats, and female rats with endogenous estrogen, or ovariectomized (OVX) rats with estrogen replacement acquire cocaine self-administration more rapidly than female rats with estrogen either surgically or chemically blocked. The purpose of this investigation was to extend the above findings to the acquisition
Megan E. Roth; Anne G. Casimir; Marilyn E. Carroll
Disruption of Reproductive Aging in Female and Male Rats by Gestational Exposure to Estrogenic Endocrine Disruptors
Polychlorinated biphenyls (PCBs) are industrial contaminants and known endocrine-disrupting chemicals. Previous work has shown that gestational exposure to PCBs cause changes in reproductive neuroendocrine processes. Here we extended work farther down the life spectrum and tested the hypothesis that early life exposure to Aroclor 1221 (A1221), a mixture of primarily estrogenic PCBs, results in sexually dimorphic aging-associated alterations to reproductive parameters in rats, and gene expression changes in hypothalamic nuclei that regulate reproductive function. Pregnant Sprague Dawley rats were injected on gestational days 16 and 18 with vehicle (dimethylsulfoxide), A1221 (1 mg/kg), or estradiol benzoate (50 ?g/kg). Developmental parameters, estrous cyclicity (females), and timing of reproductive senescence were monitored in the offspring through 9 months of age. Expression of 48 genes was measured in 3 hypothalamic nuclei: the anteroventral periventricular nucleus (AVPV), arcuate nucleus (ARC), and median eminence (females only) by real-time RT-PCR. Serum LH, testosterone, and estradiol were assayed in the same animals. In males, A1221 had no effects; however, prenatal estradiol benzoate increased serum estradiol, gene expression in the AVPV (1 gene), and ARC (2 genes) compared with controls. In females, estrous cycles were longer in the A1221-exposed females throughout the life cycle. Gene expression was not affected in the AVPV, but significant changes were caused by A1221 in the ARC and median eminence as a function of cycling status. Bionetwork analysis demonstrated fundamental differences in physiology and gene expression between cycling and acyclic females independent of treatment. Thus, gestational exposure to biologically relevant levels of estrogenic endocrine-disrupting chemicals has sexually dimorphic effects, with an altered transition to reproductive aging in female rats but relatively little effect in males.
Walker, Deena M.; Kermath, Bailey A.; Woller, Michael J.
Ornithine decarboxylase activity, nucleic acids and cell turnover in the livers of pregnant rats
1. Comparisons were made between the livers of pregnant and non-pregnant rats, all of which were fed on a ration of 20 g food per day. 2. In the second half of pregnancy there were marked increases in the weight of the liver and in its total content of protein, RNA and DNA. RNA concentration increased from the 15th day of gestation. 3. Between the 12th and 18th day of pregnancy liver weight, total RNA, totla DNA and mean liver cell nuclear volume increased in parallel at approximately the same rate of 6-10% per day. 4. Ornithine decarboxylase activity was enhanced in pregnancy by the 5th day of gestation and rose to peak activity at the 18th day. 5. The mitotic index of hepatic parenchymal cells was elevated in the first and last stages of pregnancy. The later peak in mitosis was associated with a rapid fall in mean nuclear volume. 6. There was histological evidence of cell turnover in the liver of pregnant rats; enlargement of the liver was associated with both hyperplasia and cell deletion. ImagesPlate 1
Campbell, Rosa M.; Fell, B. F.; Mackie, W. S.
Chronic stress and its effects on adrenal cortex apoptosis in pregnant rats.
Abstract The model of chronic intermittent stress by immobilization during pregnancy may produce alterations in the mechanisms that maintain adrenal gland homeostasis. In earlier investigations using this model, significant variations in plasma prolactin and corticosterone levels, and adrenal gland weights were observed. We hypothesized that chronic stress causes changes in apoptosis in the adrenal glands of pregnant rats. We identified and quantified apoptotic cells in the adrenal cortex and examined their ultrastructural characteristics using transmission electron microscopy. Adrenal glands of pregnant rats at gestation days 12, 17 and 21 were studied for control and experimental (stressed) rats. Immunolabelling techniques, stereological analysis and image quantification of adrenal gland sections were combined to determine differences in apoptosis in the different cell populations of the adrenal cortex. The apoptotic index of the experimental rats showed a significant reduction at gestation day 17, while at days 12 and 21 there were no differences from controls. Moreover, the apoptotic index of the reticular zones in control and experimental animals showed a significant increase compared to the glomerular and fascicular zones at the three gestation times studied. Chronic stress by immobilization reduced the caspase-dependent apoptotic index at gestation day 17, which may be related to variations in plasma concentrations of estrogens and prolactin. PMID:24205876
Bozzo, Aa; Sońez, Ca; Monedero Cobeta, I; Rolando, A; Romanini, Mc; Cots, D; Lazarte, Ma; Gauna, Hf; Mugnaini, Mt
Gestational hypoxia induces preeclampsia-like symptoms via heightened endothelin-1 signaling in pregnant rats.
Preeclampsia is a life-threatening pregnancy disorder. However, its pathogenesis remains unclear. We tested the hypothesis that gestational hypoxia induces preeclampsia-like symptoms via heightened endothelin-1 (ET-1) signaling. Time-dated pregnant and nonpregnant rats were divided into normoxic and hypoxic (10.5% O2 from the gestational day 6-21) groups. Chronic hypoxia had no significant effect on blood pressure or proteinuria in nonpregnant rats but significantly increased blood pressure on day 12 (systolic blood pressure, 111.7 ± 6.1 versus 138.5 ± 3.5 mm Hg; P=0.004) and day 20 (systolic blood pressure, 103.4 ± 4.6 versus 125.1 ± 6.1 mm Hg; P=0.02) in pregnant rats and urine protein (?g/?L)/creatinine (nmol/?L) ratio on day 20 (0.10 ± 0.01 versus 0.20 ± 0.04; P=0.04), as compared with the normoxic control group. This was accompanied with asymmetrical fetal growth restriction. Hypoxia resulted in impaired trophoblast invasion and uteroplacental vascular remodeling. In addition, plasma ET-1 levels, as well as the abundance of prepro-ET-1 mRNA, ET-1 type A receptor and angiotensin II type 1 receptor protein in the kidney and placenta were significantly increased in the chronic hypoxic group, as compared with the control animals. Treatment with the ET-1 type A receptor antagonist, BQ123, during the course of hypoxia exposure significantly attenuated the hypoxia-induced hypertension and other preeclampsia-like features. The results demonstrate that chronic hypoxia during gestation induces preeclamptic symptoms in pregnant rats via heightened ET-1 and ET-1 type A receptor-mediated signaling, providing a molecular mechanism linking gestational hypoxia and increased risk of preeclampsia. PMID:23817493
Zhou, Jianjun; Xiao, Daliao; Hu, Yali; Wang, Zhiqun; Paradis, Alexandra; Mata-Greenwood, Eugenia; Zhang, Lubo
Prevention of female reproductive system cancer among rural and urban Polish pregnant women.
Based on data obtained from the system MoZMaD - PL (Polish Mother and Child Health Monitoring System; an equivalent of the American system PRAMS (Pregnancy Risk Assessment Monitoring System). In the developed countries prevention programmes proved to be efficient in reducing morbidity and mortality due to breast and cervical cancer. In Poland, these diseases still constitute a very big problem, despite relatively easy and early diagnostics of pathological conditions preceding their development. The objective of the study was analysis of the usage of prophylactic examinations and the assessment of knowledge concerning risk factors of the development of reproductive cancers among pregnant women from rural and urban environments in Poland. The study was based on questionnaire forms within the Pregnancy Risk Assessment Monitoring System (MoZMaD - PL) implemented in Poland. The precise date of the study for the whole of Poland is announced annually by the Chief Sanitary Inspector. The questionnaire forms were correctly completed in 2010 by 2,877 women. The replies to the questions were introduced by surveyors into the MoZMaD - PL system central database managed by the Institute of Agricultural Medicine in Lublin. The results obtained were subjected to statistical analysis. The studies of pregnant women in Poland showed that the situation with respect to the performance of prevention examinations for cervical cancer was significantly worse among rural than urban women. Pregnant women from both rural and urban areas very rarely had breast USG performed. Awareness concerning cervical cancer risk factors was lower among rural than urban women. Also, knowledge concerning the examinations which should be performed for the prevention of breast cancer was poorer among rural, compared to urban women. The recognition of the attitudes of women at reproductive age towards prevention examinations is necessary in order to effectively plan health education and social health promotion campaigns aimed at limiting morbidity and mortality due to cancerous diseases. PMID:21736284
Bojar, Iwona; Bili?ski, Przemys?aw; Boyle, Peter; Zato?ski, Witold; Marcinkowski, Jerzy T; Wojty?a, Andrzej
Anemia treatment with darbepoetin alpha in pregnant female with chronic renal failure: report of two cases
Pregnancy is a rare finding in females with CRF. It is well known that in these cases pregnancy worsens the renal function and accelerates the beginning of dialysis therapy. Pregnancies in uremic females are complicated by a worsening of anemia as well as hypertension, fluid imbalance, electrolyte difficulties, malnutrition, polyhydramnios and preterm labor or sudden intrauterine death. The use of
Sobi?o-Jarek L; Popowska-Drojecka J; Wanic-Kossowska M; Kobelski M; Czekalski S
Propofol Exposure in Pregnant Rats Induces Neurotoxicity and Persistent Learning Deficit in the Offspring
Propofol is a general anesthetic widely used in surgical procedures, including those in pregnant women. Preclinical studies suggest that propofol may cause neuronal injury to the offspring of primates if it is administered during pregnancy. However, it is unknown whether those neuronal changes would lead to long-term behavioral deficits in the offspring. In this study, propofol (0.4 mg/kg/min, IV, 2 h), saline, or intralipid solution was administered to pregnant rats on gestational day 18. We detected increased levels of cleaved caspase-3 in fetal brain at 6 h after propofol exposure. The neuronal density of the hippocampus of offspring was reduced significantly on postnatal day 10 (P10) and P28. Synaptophysin levels were also significantly reduced on P28. Furthermore, exploratory and learning behaviors of offspring rats (started at P28) were assessed in open-field trial and eight-arm radial maze. The offspring from propofol-treated dams showed significantly less exploratory activity in the open-field test and less spatial learning in the eight-arm radial maze. Thus, this study suggested that propofol exposure during pregnancy in rat increased cleaved caspsase-3 levels in fetal brain, deletion of neurons, reduced synaptophysin levels in the hippocampal region, and persistent learning deficits in the offspring.
Xiong, Ming; Li, Jing; Alhashem, Hussain M.; Tilak, Vasanti; Patel, Anuradha; Pisklakov, Sergey; Siegel, Allan; Ye, Jiang Hong; Bekker, Alex
Effects of melamine on pregnant dams and embryo-fetal development in rats.
There are worldwide concerns regarding the potential adverse effect of melamine. This study investigated the potential effects of melamine on pregnant dams and embryo-fetal development in Sprague-Dawley rats following maternal exposure on gestational days (GD) 6-20. Melamine was administered to pregnant rats by gavage at doses of 0, 200, 400 and 800 mg kg?ą per day (n = 8-10 for each group). All dams were subjected to a Caesarean section on GD 21 and their fetuses were examined for morphological abnormalities. With administration of melamine at 800 mg kg?ą per day, maternal toxicity manifested as increased incidences of clinical signs and death, lower body weight gain and food intake, and increases in heart, adrenal gland and kidney weights. Histopathological examinations revealed an increase in incidences of congestion, tubular necrosis/degeneration, crystals, casts, inflammatory cells in tubules, tubular dilation and tubular hyaline droplets in the maternal kidneys, while fetal kidneys (one fetus/litter) did not show any histopathological changes. Developmental toxic effects included a decrease in fetal weight, an increase in the incidence of skeletal variations and a delay in fetal ossification. No treatment-related maternal or developmental effects were observed at doses ? 400 mg kg?ą per day. These results show that 15-day repeated oral dosing of melamine is embryo-/fetotoxic at a maternotoxic dose, but not teratogenic in rats. The no-observed-adverse-effect level of melamine for pregnant dams and embryo-fetal development is considered to be 400 mg kg?ą per day. PMID:21706515
Kim, Sung-Hwan; Lee, In-Chul; Lim, Jeong-Hyeon; Shin, In-Sik; Moon, Changjong; Kim, Sung-Ho; Park, Seung-Chun; Kim, Hyoung-Chin; Kim, Jong-Choon
Metabolic adaptation to pregnancy shown by increased biosynthesis of insulin in islets of Langerhans isolated from pregnant rats
MANY reports have indicated that insulin secretion is increased in pregnant women1,2 although blood sugar levels may be unchanged, indicating an increased demand for insulin in human pregnancy. Similar findings have been reported for the effects of pregnancy on insulin secretion in pregnant rats3,4 which begin to respond with a significantly increased insulin secretion at a lower glucose level than
A. J. Bone; K. W. Taylor
Quality of obstetric and midwifery care for pregnant women who have undergone female genital mutilation.
Despite the availability of professional guidelines for the pregnancy management of women affected by female genital mutilation (FGM), this study demonstrated major deficits in identification, management and safeguarding. PMID:23815196
Zenner, N; Liao, L-M; Richens, Y; Creighton, S M
Objective: To see the dose dependent effects of zinc chloride on the short-term and long-term memory in a shuttle box (rats). Methodology: Six pair adult wistar rats were taken for this experiment. One group of pregnant rats received a daily oral dose of 20mg\\/kg Zn as zinc chloride and the remaining groups received a daily oral dose of (30, 50,
Moazedi Ahmad Ali; Ghotbeddin Z; Parham GH
Hypocholesterolemic Effect of Dietary Psyllium in Female Rats
We fed cholesterol-enriched (1% cholesterol and 0.2% cholic acid) semipurified diets containing either 3% cellulose or psyllium to 2 groups of female Wistar rats for a period of 8 weeks. The feeding of the cholesterol-enriched semipurified diets resulted in a progressive increase in plasma cholesterol levels in both groups during the 8 weeks of the experiment. The rats fed psyllium,
A. H. M. Terpstra; J. A. Lapré; H. T. de Vries; A. C. Beynen
Aspects of the Development of Housing for the Spaceflight of Pregnant and Lactating Rats with Neonates
NASA Technical Reports Server (NTRS)
Recent and upcoming spaceflights are investigating the effect of weightlessness on developing neural and organ systems. Pregnant rats and dams with neonates have to be accommodated in cages that support the special requirements of these animals. Extensive ground testing of cage concepts, the effect of launch and landing stresses on the maintenance of pregnancy and maternal behavior at different neonatal ages, and techniques for monitoring adaptability to change are discussed. A spaceflight opportunity for the NlH.R3 payload of rat families at three different postnatal ages demonstrated that the survival of very young animals was not good but that older newborns could be returned to Earth in reasonably good health. The development of cages for the Research Animal Holding Facility (RAHF) to support the flight of neonates on Neurolab was continued and incorporated modifications that were demonstrated by the NIH.R3 flight. Other modifications to the RAHF are discussed. Data from biocompatibility and experiment verification testing are presented.
Hinds, William E.; Mayer, David J.; Evans, Juli; Spratt, Shahn; Lane, Philip K.; Rodriguez, Shari L.; Navidi, Meena; Armstrong, Rachel; Lemos, Bonnie; Dalton, Bonnie P. (Technical Monitor)
Dose-response effects of diphenylhydantoin on pregnant dams and embryo-fetal development in rats.
Despite the widespread use of diphenylhydantoin (DPH), there is a lack of reliable information on the teratogenic effects, correlation with maternal and developmental toxicity, and dose-response relationship of DPH. This study investigated the dose-response effects of DPH on pregnant dams and embryo-fetal development as well as the relationship between maternal and developmental toxicity. DPH was orally administered to pregnant rats from gestational days 6 through 15 at 0, 50, 150, and 300 mg/kg/day. At 300 mg/kg, maternal toxicity including increased clinical signs, suppressed body weight, decreased food intake, and increased weights of adrenal glands, liver, kidneys, and brain were observed in dams. Developmental toxicity, including a decrease in fetal and placental weights, increased incidence of morphological alterations, and a delay in fetal ossification delay also occurred. At 150 mg/kg, maternal toxicity manifested as an increased incidence of clinical signs, reduced body weight gain and food intake, and increased weights of adrenal glands and brain. Only minimal developmental toxicity, including decreased placental weight and an increased incidence of visceral and skeletal variations, was observed. No treatment-related maternal or developmental effects were observed at 50 mg/kg. These results show that DPH is minimally embryotoxic at a minimal maternotoxic dose (150 mg/kg/day) but is embryotoxic and teratogenic at an overt maternotoxic dose (300 mg/kg/day). Under these experimental conditions, the no-observed-adverse-effect level of DPH for pregnant dams and embryo-fetal development is considered to be 50 mg/kg/day. These data indicate that DPH is not a selective developmental toxicant in the rat. PMID:22887608
Kim, Sung-Hwan; Lee, In-Chul; Baek, Hyung-Seon; Lim, Jeong-Hyeon; Moon, Changjong; Shin, Dong-Ho; Kim, Sung-Ho; Park, Seung-Chun; Kim, Jong-Choon
Hepatic bile acids and bile acid-related gene expression in pregnant and lactating rats.
Background. Significant physiological changes occur during pregnancy and lactation. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease closely related to disruption of bile acid homeostasis. The objective of this study was to examine the regulation of bile acid synthesis and transport in normal pregnant and lactating rats. Materials and Methods. Livers from timed pregnant SD rats were collected on gestational days (GD) 10, 14 and 19, and postnatal days (PND) 1, 7, 14 and 21. Total bile acids were determined by the enzymatic method, total RNA was isolated and subjected to real time RT-PCR analysis. Liver protein was extracted for western-blot analysis. Results. Under physiological conditions hepatic bile acids were not elevated during pregnancy but increased during lactation in rats. Bile acid synthesis rate-limiting enzyme Cyp7a1 was unchanged on gestational days, but increased on PND14 and 21 at mRNA and protein levels. Expression of Cyp8b1, Cyp27a1 and Cyp7b1 was also higher during lactation. The mRNA levels of small heterodimer partner (SHP) and protein levels of farnesoid X receptor (FXR) were increased during pregnancy and lactation. Bile acid transporters Ntcp, Bsep, Mrp3 and Mrp4 were lower at gestation, but increased during lactation. Hepatic Oatp transporters were decreased during pregnancy and lactation. Conclusion. Hepatic bile acid homeostasis is maintained during normal pregnancy in rats, probably through the FXR-SHP regulation. The expression of bile acid synthesis genes and liver bile acid accumulation were increased during lactation, together with increased expression of bile acid efflux transporter Bsep, Mrp3 and Mrp4. PMID:24010021
Zhu, Qiong N; Xie, Hong M; Zhang, Dan; Liu, Jie; Lu, Yuan F
Seizures and reproductive function: insights from female rats with epilepsy
OBJECTIVE Chronic seizures in women can have adverse effects on reproductive function, such as polycystic ovarian syndrome (PCOS), but it has been difficult to dissociate the effects of epilepsy per se from the role of antiepileptic drugs (AEDs). To distinguish the effects of chronic seizures from AEDs, we used the laboratory rat, where an epileptic condition can be induced without concomitant AED treatment. METHODS Adult female rats were administered the chemoconvulsant pilocarpine to initiate status epilepticus (SE), which was decreased in severity by the anticonvulsant diazepam. These rats developed spontaneous seizures in the ensuing weeks, and are therefore termed "epileptic." Controls were saline-treated rats, or animals that were injected with pilocarpine but did not develop SE. Ovarian cyclicity and weight gain were evaluated for 2-3 months. Serum hormone levels were assayed from trunk blood, collected at the time of death. Paraformaldehyde-fixed ovaries were evaluated quantitatively. RESULTS Rats that had pilocarpine-induced seizures had an increased incidence of acyclicity by the end of the study, even if SE did not occur. Ovarian cysts and weight gain were significantly greater in epileptic rats than controls, whether rats maintained cyclicity or not. Serum testosterone was elevated in epileptic rats, but estradiol, progesterone and prolactin were not. INTERPRETATIONS The results suggest that an epileptic condition in the rat leads to increased body weight, cystic ovaries and elevated testosterone levels. Although caution is required when comparing female rats to women, the data suggest that epilepsy per se may be sufficient to induce abnormalities in the control of the ovary.
Scharfman, Helen E.; Kim, Michelle; Hintz, Tana M.; MacLusky, Neil J.
Voiding function in obese and type 2 diabetic female rats.
The effects of obesity and type 2 diabetes (DMII) on the lower urinary tract (LUT) were characterized by evaluating voiding function and anatomy in female Zucker diabetic fatty (ZDF) rats. Age-matched female virgin rats were separated into three experimental groups: Zucker lean rats (control; normal diet, n = 22), ZDF rats (obese+nondiabetic; low-fat diet, n = 22), and ZDF rats (obese+diabetic; high-fat diet, n = 20). Rats were placed on their specified diet for 10 wk before urodynamic LUT evaluation. A suprapubic catheter was implanted 2 days before urodynamic studies. Voiding function was evaluated by cystometric and leak point pressure (LPP) testing. The bladder, urethra, and vagina were immediately excised for qualitative histological evaluation. Compared with control rats, obese+nondiabetic and obese+diabetic rats had significantly decreased contraction pressure (P = 0.003) and increased cystometric filling volume (P < 0.001). Both obese groups exhibited significantly higher voided volumes (P = 0.003), less frequent urinary events (P < 0.001), and increased residual volumes (P = 0.039). LPP studies showed a nonsignificant decrease in LPP (P = 0.075) and baseline pressure (P = 0.168) in both obese groups compared with control. Histology of the external urethral sphincter in obese rats showed increased fibrosis, leading to disruption of the skeletal muscle structure compared with control. Additionally, the bladder wall of the obese+nondiabetic and obese+diabetic rats demonstrated edema and vasculopathy. Voiding dysfunction was evident in both obese groups but with no significant differences due to DMII, suggesting that voiding dysfunction in DMII may be attributable at least in part to chronic obesity. PMID:19889955
Gasbarro, Gregory; Lin, Dan Li; Vurbic, Drina; Quisno, Amanda; Kinley, Bruce; Daneshgari, Firouz; Damaser, Margot S
Mirex Induces Ornithine Decarboxylase in Female Rat Liver.
National Technical Information Service (NTIS)
Ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, was significantly induced in female rat liver following oral administration of the pesticide, mirex. After dual oral exposure (120 mg/kg; 21 and 4 hrs. prior to sacrifice) ind...
A. Mitra I. Richards K. Kitchin R. Conolly A. P. Kulkarni
During chronic treatment of weanling female rats with daily injections (0.069 mmol/kg of gamma-hexachlorocyclohexane (lindane, gamma-HCH), the treatment induced a significant 20% increase in body weight after 110 days. Further investigation with 0, 5, 10, 20 and 40 mg/kg lindane ...
Estrogen Abolishes Latent Inhibition in Ovariectomized Female Rats
ERIC Educational Resources Information Center
Estrogen is frequently prescribed as a method of birth control and as hormone replacement therapy for post-menopausal women with varied effects on cognition. Here the effects of estrogen on attention were examined using the latent inhibition (LI) behavioral paradigm. Ovariectomized (OVX) female rats were given either estrogen benzoate (EB, 10 or…
Nofrey, Barbara S.; Ben-Shahar, Osnat M.; Brake, Wayne G.
Tumorigenic effects of dichloroacetic acid in female F344 rats
Introduction: Dichloroacetic acid (DCA) is a halogenated organic acid produced during oxidant disinfection of drinking water. Prior studies indicate that DCA may increase liver tumors in mice. Here we evaluated the hepatic tumorigenicity of DCA in female rats when given alone ...
Effects of Nicotine Withdrawal in Adult Male and Female Rats.
National Technical Information Service (NTIS)
Gender differences have been observed in difficulty quitting smoking. A rodent model of nicotine withdrawal has been used by several laboratories, but only in males. Nicotine withdrawal in male and female adult rats was examined in a dimly-lit, comfortabl...
K. R. Hamilton
Metabolism and Disposition of Bisphenol A in Female Rats
Bisphenol A (BPA), which is used in the manufacture of polycarbonates, elicits weak estrogenic activity in in vitro and in vivo test systems. The objectives of this study were to compare the patterns of disposition of radioactivity in adult female F-344 and CD rats after oral administration of 14C BPA (100 mg\\/kg), to isolate the glucuronide of BPA and to
Rodney W. Snyder; Susan C. Maness; Kevin W. Gaido; Frank Welsch; Susan C. J. Sumner; Timothy R. Fennell
Ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, was significantly induced in female rat liver following oral administration of the pesticide, mirex. fter dual oral exposure (120 mg/kg; 21 and 4 hrs prior to sacrifice) induction of ODC activity in r...
3. Impact of altered gravity on CNS development and behavior in male and female rats
NASA Astrophysics Data System (ADS)
The present study examined the effect of altered gravity on CNS development. Specifically, we compared neurodevelopment, behavior, cerebellar structure and protein expression in rat neonates exposed perinatally to hypergravity. Pregnant Sprague-Dawley rats were exposed to 1.5G-1.75G hypergravity on a 24-ft centrifuge starting on gestational day (G) 10, through giving birth on G22/G23, and nursing their offspring through postnatal day (P) 21. Cerebellar mass on P6 was decreased in 1.75G-exposed male pups by 27.5 percent; in 1.75G-exposed female pups it was decreased by 22.5 percent. The observed cerebellar changes were associated with alterations in neurodevelopment and motor behavior. Exposure to hypergravity impaired performance on the following neurocognitive tests: (1) righting time on P3 was more than doubled in 1.75G-exposed rats and the effect appeared more pronounced in female pups, (2) startle response on P10 was delayed in both male and female HG pups; HG pups were one-fifth as likely to respond to a clapping noise as SC pups, and (3) performance on a rotorod on P21 was decreased in HG pups; the duration of the stay on rotorod recorded for HG pups of both sexes was one tenth of the SC pups. Furthermore, Western blot analysis of selected cerebellar proteins suggested gender-specific changes in glial and neuronal proteins. On P6, GFAP expression was decreased by 59.2 percent in HG males, while no significant decrease was observed in female cerebella. Synaptophysin expression was decreased in HG male neonates by 29.9 percent and in HG female neonates by 20.7 percent as compared to its expression in SC cerebella. The results of this experiment suggest that perinatal exposure to hypergravity affects cerebellar development and behavior differently in male and female neonates. If one accepts that hypergravity is a good paradigm to study the effect of microgravity on the CNS, and since males and females were shown to respond differently to hypergravity, it can be surmised that males and females may respond differently to the microgravity encountered in space. Supported by NIEHS grant ES11946-01 awarded to E. S-S.
Sajdel-Sulkowska, E. M.; Nguon, K.; Ladd, B.; Sulkowski, V. A.; Sulkowski, Z. L.; Baxter, M. G.
Altered pancreatic morphology in the offspring of pregnant rats given reduced dietary protein is time and gender specific.
Restriction of dietary protein during gestation and lactation in the rat results in a reduction in beta cell mass, insulin content and release in the offspring, and glucose intolerance when the offspring reach adulthood. The present study was designed to identify if a particular developmental window existed during prenatal development when endocrine pancreatic development was most susceptible to nutritional insult. Pregnant rats received a low-protein (8%, LP), but isocalorific diet from conception to parturition, during the first 2 weeks of gestation (LP (1-2)), the second week only (LP (2)), or the third week (LP (3)). At other times, they received a 20% protein (C) diet, while control animals received this diet continuously. When the offspring were examined at 130 days age, animals that had received LP diet had a significantly impaired glucose tolerance compared with control-fed animals. Pancreatic morphology was examined in the offspring on postnatal days 1 and 21. The LP diet resulted in a significant decrease in the numbers of large (more than 10 000 microm(2)) and medium (between 5000 and 10 000 microm(2)) sized islets present at postnatal day 1 for all LP treatments. Consequently, mean islet area and the mean number of beta cells were reduced. The impact of LP diet was most pronounced in LP (2) for females and in LP (3) for males, and this was greater than for continuous LP exposure. Insulin and Glut-2 mRNA expression were impacted negatively by LP in early and late gestation, but increased following administration in mid-gestation. Total pancreatic insulin content was not altered by LP treatment. Pdx-1, a transcription factor associated with both beta cell development and insulin gene transcription, was decreased in female offspring following LP (1-2) and LP (3), but not in males. Pancreatic expression of nestin mRNA, and the abundance of nestin-immunoreactive cells within islets, was decreased by all LP treatments. By postnatal day 21, the mean islet area and number of beta cells had largely recovered. However, insulin and Glut-2 mRNAs were elevated in offspring exposed to LP diet, particularly in females. The studies show that LP dietary insult in early, middle, or late gestation, all result in a relative deficiency of beta cells following birth, due to a failure to develop larger islets, but that females were particularly susceptible in mid-gestation and males in late gestation. PMID:17065391
Chamson-Reig, Astrid; Thyssen, Sandra M; Arany, Edith; Hill, David J
Immune stress in late pregnant rats decreases length of gestation and fecundity, and alters later cognitive and affective behaviour of surviving pre-adolescent offspring
Immune challenge during pregnancy is associated with preterm birth and poor perinatal development. The mechanisms of these effects are not known. 5?-Pregnan-3?-ol-20-one (3?,5?-THP), the neuroactive metabolite of progesterone, is critical for neurodevelopment and stress responses, and can influence cognition and affective behaviours. To develop an immune challenge model of preterm birth, pregnant Long–Evans rat dams were administered lipopolysaccharide [LPS; 30 ?g/kg/ml, intraperitoneal (IP)], interleukin-1? (IL-1?; 1 ?g/rat, IP) or vehicle (0.9% saline, IP) daily on gestational days 17–21. Compared to control treatment, prenatal LPS or IL-1? reduced gestational length and the number of viable pups born. At 28–30 days of age, male and female offspring of mothers exposed to prenatal IL-1? had reduced cognitive performance in the object recognition task compared to controls. In females, but not males, prenatal IL-1? reduced anxiety-like behaviour, indicated by entries to the centre of an open field. In the hippocampus, progesterone turnover to its 5?-reduced metabolites was lower in prenatally exposed IL-1? female, but not in male offspring. IL-1?-exposed males and females had reduced oestradiol content in hippocampus, medial prefrontal cortex and diencephalon compared to controls. Thus, immune stress during late pregnancy reduced gestational length and negatively impacted birth outcomes, hippocampal function and central neurosteroid formation in the offspring.
Decrease of sexual receptivity by prolylendopeptidase inhibitor in female rats.
The effects of a prolylendopeptidase inhibitor, 1-[3-(2-indanylanylacetyl)-L-thioprolyl]pyrrolidine (Z-321), on lordosis behavior were investigated in estrogen and progesterone-treated ovariectomized rats. Females were orally administered 100, 200 or 300 mg/kg Z-321 or the vehicle (control). The mean lordosis quotient in the rats given 300 mg/kg Z-321 was lower than that in control group, but that in rats given 100 or 200 mg/kg Z-321 was not lower. Thus, Z-321 suppressed lordosis in estrogen and progesterone-treated ovariectomized rats. Peptide neurotransmitters, especially those containing proline, are thought to be involved in the inhibitory mechanisms for lordosis behavior. PMID:10887944
Oosuka, I; Tanaka, Y; Miura, N; Yamanouchi, K
Effects of short and long term treatment of Ballota undulata on female albino rats fertility and pregnancy.
The objectives of this study is to investigate the toxic effects of Ballota undulata (300 mg kg(-1) b.wt.) on the reproductive system after administration to female Sprague-Dawley rats for two time periods 4 and 12 weeks. Forty adult female Sprague-Dawley rats were divided into two treatment and two control groups of 10 rats each. The two treated groups received 15 mg kg(-1) b.wt. of Ballota undulata for two periods of 4 and 12 weeks. Female rats were allowed mating with males after treatment. Several pregnancy parameters were investigated including: total number of pregnant rats, body weight and reproductive organ weight, number of implantation sites, number of resorption sites and number of viable fetuses. The significance of these results was calculated using student's t and Chi-square tests. Exposure to Ballota undulata for 4 weeks did not have significant effects on most parameters investigated. However, a slight decrease in the relative ovarian and embryo weights was observed. Administration of Ballota undulata for 12 weeks significantly reduced the percentage of pregnancies and the number of implantation sites when compared with controls. In addition, a decrease in ovarian weights and in viable fetuses' number was also observed. Histological sections of ovaries of female treated with Ballota undulata were found to have congested blood vessels in cortical and medullary regions. We also noted the arrestment of developing follicles at primary and secondary stages in addition to presence of degenerative areas and hypercellullarity in medulla. Long term treatment with Ballota undulata might lead to diversified negative effects on fertility and pregnancy in female rats. PMID:18817140
Qazan, Walid Sh
Suppression of myometrial contractile responses to oxytocin after different durations of chronic hypoxia in the near-term pregnant rat
Objective: In light of our previous finding that chronic hypoxia decreases the myometrial contractile response to oxytocin in the near-term pregnant rat, we designed the current study (1) to investigate the effect of duration of hypoxic exposure on the contractile response to oxytocin and oxytocin binding sites and (2) to examine the effect of prolonged hypoxia on the contractile response
Joon W. Rhee; Lubo Zhang; Charles A. Ducsay
The effect of exercise on carbohydrate preference in female rats.
Exercise has a myriad of health benefits, including positive effects against heart disease, diabetes, and dementia. Cognitive performance improves following chronic exercise, both in animal models and humans. Studies have examined the effect of exercise on feeding, demonstrating a preference towards increased food consumption. Further, sex differences exist such that females tend to prefer carbohydrates over other macronutrients following exercise. However, no clear effect of exercise on macronutrient or carbohydrate selection has been described in animal or human studies. This research project sought to determine the effect of voluntary exercise on carbohydrate selection in female rats. Preference for a complex (starch) versus a simple (dextrose) carbohydrate was assessed using a discriminative preference to context paradigm in non-exercising and voluntarily exercising female rats. In addition, fasting blood glucose and performance in the Morris water task was examined in order to verify the effects of exercise on performance in this task. Female rats given access to running wheels preferred a context previously associated with starch, whereas females with no running wheel access preferred a context previously associated with dextrose. No changes in blood glucose were observed. However, cognitive differences in the Morris water task were observed such that voluntary exercise allowed rats to find a new location of a hidden platform following 4 days of training to an old platform location. These results suggest that voluntary exercise may decrease preservative behaviors in a spatial navigation task through the facilitation of plasticity mechanisms. This study is the first of its kind to demonstrate the influence of exercise on taste preference for complex and simple carbohydrates with this context conditioning paradigm. PMID:24406468
Keeley, R J; Zelinski, E L; Fehr, L; McDonald, R J
Prenatal corticosterone treatment induces long-term changes in spontaneous and apomorphine-mediated motor activity in male and female rats
The potential influence of glucocorticoids on fetal brain development was investigated after corticosterone administration via pellets to pregnant rats during the last trimester of gestation. We examined both spontaneous motor activity and dopamine-mediated motor responses to apomorphine, a predominantly D1 and D2 receptor agonist, given at a postsynaptic dose (1mg\\/kg, s.c.) to both prepubertal and adult male and female offspring.
R Diaz; K Fuxe; S. O Ögren
Differences in Behavioral Parameters of Long-Term Pain in Formalin Test at the Period of Sex Maturation in Prenatally Stressed Female and Male Rats
The effect of immobilization of pregnant rats was studied on parameters of the specific biphasic behavioral response (BBR) (patterns of flexion, shaking, licking, duration of the phases and of the interphase interval), of which the first phase characterizes the acute, while the second, he long-term pain in a nociceptive formalin test in the 40-day old female and male off-spring. The
I. P. Butkevich; E. A. Vershinina; V. A. Mikhailenko; M. N. Leontieva
Adolescent cannabinoid treatment negatively affects reproductive behavior in female rats.
Sex differences in the neurobehavioral effects of chronic cannabinoid exposure suggest that gonadal hormones may modify cannabinoid activity. The current experiment assessed the impact of combined cannabinoid and estradiol treatment in ovariectomized, adolescent female rats on subsequent adult sexual behavior. Female Long-Evans rats were administered daily injections of either the cannabinoid agonist, CP 55,940 (0.4 mg/kg), or vehicle from post-natal day (PND) 40-49. Half of each treatment group also received daily injections of estradiol (50 ?g/kg) or sesame oil vehicle from PND 39-49. Beginning on PND 74, subjects' reproductive behavior, including receptivity, proceptivity, and pacing, was assessed via a fifteen-minute paced mating test. There were significant main effects of estradiol treatment on rate of hop-darts emitted, number of arena crossings, and ejaculations received during the paced mating test. Overall, estradiol-treated females produced higher and more typical levels of sexual behavior. There were significant interactions between hormone and cannabinoid treatment on lordosis quotient, percentage of exits following male sexual stimulation, and contact-return latency for intromissions. Adolescent cannabinoid treatment detrimentally impacted the display of female receptivity and pacing, but only within estradiol-treated subjects. We discuss possible interpretations of these results, including potential mechanisms by which adolescent cannabinoid exposure might disrupt the normal development of female reproductive behavior. PMID:24120423
Minney, Sarah M; López, Hassan H
Clitoral anesthesia disrupts paced copulation in the female rat.
Clitoral stimulation produced by sexual contact with a partner or during manual stimulation is associated with pleasure in humans, and produces conditioned place preference in rats. The present experiment investigated the effect of blocking genitosensory stimulation of the clitoris with lidocaine during copulation in female rats on a measure of female sexual motivation: pacing behavior. Sexually naďve, ovariectomized female rats were treated with 10?g estradiol benzoate 48h and 500?g progesterone 4h prior to a 30-min copulatory trial with a sexually vigorous stimulus male scheduled every 4days. A total of 10 copulatory sessions were divided into two phases of 5 trails each. In the first phase, females received an injection (0.05ml) of either 2% lidocaine, saline, or no injection to the clitoral sheath under isoflurane anesthesia immediately prior to the start of a copulatory session, and were then placed on one side of a paced mating chamber and allowed to copulate for 30min. In the second phase, females previously injected with lidocaine were switched to saline and vice versa, and the no injection group remained the same. Variables measured included overall time spent with the males, number of solicitations, contact-return latencies following male mounts, intromissions, and ejaculations; the frequency of entrances and exits from the male chamber, and frequency of mounts, intromissions, ejaculations. Sexual behavior was examined at session 1, session 5, and session 10. At test 5, females that received LID had a greater number of entrances/exits but spent significantly less time in the presence of the male during the copulatory bout than CNTL animals. These females also displayed a trend for longer contact return latencies s after ejaculations than VEH and CNTL groups. On session 10, females that received LID and subsequently switched to VEH treatment no longer differed from controls in entrance/exit numbers, time spent with males or ejaculation contact return latency. They did however, receive a greater number of intromissions and displayed shorter inter intromission intervals compared to CNTLs. We suggest that clitoral stimulation in the rat serves as both a reward signal and may contribute to the detection of differences in copulatory stimuli that are critical to pacing and potentially, the initiation of pregnancy. PMID:24176775
Parada, M; Sparks, L M; Censi, S; Pfaus, J G
T-2 Toxin-induced Toxicity in Pregnant Mice and Rats
T-2 toxin is a cytotoxic secondary fungal metabolite that belongs to the trichothecene mycotoxin family. This mycotoxin is a well known inhibitor of protein synthesis through its high binding affinity to peptidyl transferase, which is an integral part of the ribosomal 60s subunit, and it also inhibits the synthesis of DNA and RNA, probably secondary to the inhibition of protein synthesis. In addition, T-2 toxin is said to induce apoptosis in many types of cells bearing high proliferating activity. T-2 toxin readily passes the placenta and is distributed to embryo/fetal tissues, which include many component cells bearing high proliferating activity. This paper reviews the reported data related to T-2 toxin-induced maternal and fetal toxicities in pregnant mice and rats. The mechanisms of T-2 toxin-induced apoptosis in maternal and fetal tissues are also discussed in this paper.
Doi, Kunio; Ishigami, Noriaki; Sehata, Shinya
Simulated conditions of microgravity suppress progesterone production by luteal cells of the pregnant rat
NASA Technical Reports Server (NTRS)
The purpose of this study was to assess whether simulated conditions of microgravity induce changes in the production of progesterone by luteal cells of the pregnant rat ovary using an in vitro model system. The microgravity environment was simulated using either a high aspect ratio vessel (HARV) bioreactor with free fall or a clinostat without free fall of cells. A mixed population of luteal cells isolated from the corpora lutea of day 8 pregnant rats was attached to cytodex microcarrier beads (cytodex 3). These anchorage dependent cells were placed in equal numbers in the HARV or a spinner flask control vessel in culture conditions. It was found that HARV significantly reduced the daily production of progesterone from day 1 through day 8 compared to controls. Scanning electron microscopy showed that cells attached to the microcarrier beads throughout the duration of the experiment in both types of culture vessels. Cells cultured in chamber slide flasks and placed in a clinostat yielded similar results when compared to those in the HARV. Also, when they were stained by Oil Red-O for lipid droplets, the clinostat flasks showed a larger number of stained cells compared to control flasks at 48 h. Further, the relative amount of Oil Red-O staining per milligram of protein was found to be higher in the clinostat than in the control cells at 48 h. It is speculated that the increase in the level of lipid content in cells subjected to simulated conditions of microgravity may be due to a disruption in cholesterol transport and/or lesions in the steroidogenic pathway leading to a fall in the synthesis of progesterone. Additionally, the fall in progesterone in simulated conditions of microgravity could be due to apoptosis of luteal cells.
Bhat, G. K.; Yang, H.; Sridaran, R.
[Behavioral effects of ketanserine in prenatally stressed female rats].
Comparative study of the effects of chronic administration of 5-HT(2A/2C)-receptors agonist (m-CPP, 0.5 mg/kg, i.p.) and 5-HT(2A/2C)-receptors antagonist (ketanserine, 0.1 mg/kg, i.p.) for 14 days on the anxiety- and depression-like behavior in adult prenatally stressed female rats showed that prenatal stress increased the anxiety level in female rats. Chronic administration of ketanserine produced anxiolytic and antidepressant effects, which inhibited the negative action of prenatal stress on the emotional behavior, whereas chronic administration of m-CPP did not change the emotional behavior. PMID:22442956
Fedotova, Iu O; Pivina, S G; Ordian, N E
Behavioral sensitization to nicotine in female and male rats
Behavioral sensitization to nicotine has been studied in both male and female rats, but studies up to now have been difficult\\u000a to compare due to different experimental conditions. Including both sexes in scientific research is of great importance since\\u000a clinical data indicate gender differences both in response to nicotine and in ability for smoking cessation. The aim of the\\u000a present
Mia Ericson; Gunilla Norrsjö; Anders I. Svensson
Ovarian hormone withdrawal-induced "depression" in female rats.
Approximately 15% of child-bearing women develop postpartum depression (PPD), and many women with PPD experience anxious symptoms. It has been proposed that PPD is precipitated by the dramatic decline in reproductive hormones that occurs just after childbirth. To examine this hypothesis, ovariectomized female Sprague-Dawley rats underwent a hormone-simulated pregnancy (HSP) regimen; during the subsequent hormone withdrawal period, rats were tested in the forced swim test or elevated plus-maze, animal models of depression and anxiety, respectively. The HSP regimen consisted of injections with progesterone and escalating doses of estradiol benzoate for 22 days; control rats received daily vehicle injections. One, two, four or seven days after the last hormone injection, separate groups of rats were tested once on either the forced swim test or the elevated plus-maze. To examine any hormone withdrawal-induced changes in activity levels, spontaneous locomotor activity was measured at the same time points. At 2 and 4 days after the last hormone injection, HSP-treated females displayed significant increases in immobility relative to vehicle-treated females in the forced swim test. Behavior on the elevated plus-maze did not differ between the HSP and control groups at any of the withdrawal time points. There were also no differences in spontaneous locomotor activity between the HSP and control females at any of the withdrawal time points. The results of this study suggest that postpartum hormone withdrawal may contribute to depressive symptoms experienced after giving birth, and that the HSP-hormone withdrawal protocol may provide a useful animal model of PPD. PMID:15581673
Stoffel, Erin C; Craft, Rebecca M
Decreased duration of pentobarbital-induced narcosis in immature and adult female rats prenatally exposed to cimetidine
The effect of prenatal cimetidine exposure (PreCM) on the duration of pentobarbital-induced narcosis (DPN) was assessed in immature (14- and 28-day old) and adult (50-60-day old) male and female rats. PreCM exposure was accomplished by treating mothers with cimetidine (CM) (20 mg/kg, ip) daily for the last two days of gestation and then (0.01% in drinking water) throughout lactation. Pregnant mothers of untreated offspring (Con) received saline. PreCM decreased DPN to 505 +/- 33 min (from 611 +/- 23 min in Con) and 393 +/- 190 min (from 686 +/- 44 min in Con) in 14-day old male and female rats, respectively. Similarly, PreCM decreased DPN to 88 +/- 15 min (from 134 +/- 3 min in Con) and 102 +/- 19 min (from 171 +/- 44 min in Con) in 28-day old male and female rats, respectively. At 21 days, PreCM did not alter DPN in either sex. At 50-60 days, however, it decreased DPN to 144 +/- 41 min (from 238 +/- 7 min in Con) in females but had no effect in males; PreCM also increased the plasma clearance of administered /sup 14/C-pentobarbital more in females than in males. The effects of PreCM, particularly the long-term effects, were most prominent in female rats and were the opposite of those of postnatal treatment with CM. The results together with those of studies with hepatic microsomes suggest that PreCM may have resulted in the induction of hepatic drug-metabolizing enzymes during the perinatal period.
Donnelly, D.A.; Iba, M.M.
A low-affinity estrogen-binding site in pregnant rat uteri: analysis and partial purification.
We have identified a low-affinity (type II) estrogen-binding site (EBS) that is expressed at high levels during pregnancy in rat uteri. Although this activity was detectable in nonpregnant rat uteri, it was present in amounts (0.094 pmol/g of uteri) that were severalfold lower than the high-affinity type I estrogen receptor (0.57 pmol/g of uteri). During pregnancy, at 19-20 days of gestation, the low-affinity type II EBS became the major (> or = 88%) estrogen-binding site in rat uteri. The increase in the level of low-affinity EBS (7.9 pmol/g) in uteri was approximately 85-fold with an approximately 20-fold increase in the specific activity (0.39 pmol/mg) of this form, whereas the high-affinity form remained relatively unchanged. We report here a method of purification of type II EBS from pregnant rat uteri and present an analysis of its DNA and steroid-binding properties. Estradiol-binding studies and Scatchard analysis showed that the type II EBS had an apparent estradiol-binding affinity of > or = 24 nM. Gel filtration and SDS/PAGE analysis indicated that the type II EBS was a monomeric 73-kDa protein. The estradiol binding remained apparently uninhibited in the presence of a large excess of tamoxifen, nafoxidine, or dihydrotestosterone. Estradiol, diethylstilbestrol, and quercitin (a type II EBS-specific inhibitor) competed efficiently. The purified low-affinity EBS did not have sequence-specific DNA-binding activity with the estrogen-responsive element, which indicated that it differs in function from the type I estrogen receptor. Images
Gray, W G; Biswas, E E; Bashirelahi, N; Biswas, S B
Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic response to a nitric oxide donor in the pregnant rat
Pregnancy is characterized by plasma volume expansion and renal sodium retention with loss of natriuretic response to atrial natriuretic peptide due to increased medullary phosphodiesterase-5 (PDE5). Here, we determined whether natriuretic responses to nitric oxide (NO) are also blunted in pregnancy due to increased PDE5. Anesthetized 16-day pregnant and virgin rats were studied at baseline and during intrarenal infusion of the NO donor spermine NONOate (2.5 nmol/min), the PDE5 inhibitor sildenafil (SILD; 0.5 ?g/min), or a combination. The right (noninfused) kidney served as a control. Intrarenal NONOate had no effect on mean arterial pressure (MAP); however, SILD reduced MAP in virgin rats, and the combination of NONOate+SILD reduced MAP in both virgin and pregnant rats. Neither NONOate nor SILD altered glomerular filtration rate. NONOate and SILD each stimulated sodium excretion (UNaV) and fractional excretion of sodium (FENa) in virgin rats, but the combination did not result in an additional natriuretic response. However, NONOate infusion did not increase UNaV or FENa in pregnant rats, but the natriuretic response to NONOate was restored with SILD, and SILD alone produced a natriuresis during pregnancy. Sodium nitroprusside (10?4 mol/l)-stimulated cGMP accumulation from inner medullary collecting duct cells was blunted in cells from pregnant vs. virgin or postpartum rats and was restored by treatment with the PDE5 inhibitor DMPPO (10?7 mol/l). Therefore, increased intrarenal PDE5 mediates the blunted natriuretic response to NO, and loss of responsiveness to the cGMP-dependent, natriuretic agents may contribute to volume expansion during pregnancy.
Ni, Xi-Ping; Humphreys, Michael H.; Baylis, Chris
Cytotoxic effect of aspartame (diet sweet) on the histological and genetic structures of female albino rats and their offspring.
The present study evaluated the effect of aspartame intake on the histological and genetic structures of mother albino rats and their offspring. Sixty adult female albino rats and 180 of their offspring were equally divided into two groups (control and treated), each group divided into three subgroups. Each subgroup consisted of 10 pregnant rats and 30 of their offspring. The experimental design divided into three periods: (1) the gestation period (subgroup one), (2) the gestation period and three weeks after delivery (subgroup two) and (3) animals in the third subgroup treated as subgroup two then left till the end of the ninth week after delivery. Each pregnant rat in the treated subgroups was given a single daily dose of 1 mL aspartame solution (50.4 mg) by gastric gavage throughout the time intervals of experimental design. At the end of each experimental period for control and treated subgroups, the liver of half of both control and treated groups were subjected for histological study while the liver and bone marrow of the other halves were subjected for cytogenetic studies. Body weight of both groups were recorded individually twice weekly in the morning before offering the diet. The results revealed that the rats and their offspring in the subgroups of control animals showed increases in body weight, normal histological sections, low chromosomal aberration and low DNA fragmentation. The treated animals in the three subgroups rats and their offspring revealed decreases in body weight, high histological lesions, increases in the chromosomal aberration and DNA fragmentation compared with control groups. In conclusion, the consumption of aspartame leads to histopathological lesions in the liver and alterations of the genetic system in the liver and bone marrow of mother albino rats and their offspring. These toxicological changes were directly proportional to the duration of its administration and improved after its withdrawal. PMID:24159687
Abd Elfatah, Azza A M; Ghaly, Inas S; Hanafy, Safaa M
Effects of massive doses of ergocalciferol plus cholesterol on pregnant rats and their offspring.
Ergocalciferol (320,000 or 480,000 IU/kg) plus cholesterol (60 mg/kg) in olive oil solution was administered daily on 1, 2, or 4 consecutive days to pregnant rats from 9,10, 14, or 18 of gestation. The control animals received only olive oil. Disseminated lesions of metastic calcinosis were found in various tissues, in the coronary arteries and myocardium, in the media of the abnormal aorta, in the lung and pleura, in the gastoinstestinal tract, and in the kidney. This is in contrast to the atherosclerosis described in nonpregnant rats fed a similiar diet. A significant decline in maternal weight as well as a high rate of morbidity and mortality was observed. In mothers killed on day 22 of pregnancy, fetal and placental growths appeared significantly retarded suggesting a direct effect of the steroid or its more active metabolite, 1,25-dihydroxycholecalciferol, on the fetus or the trophoblastic tissue. Fetal bone lesionsassociated with a generalized retardation of ossification, placental edema, or calcification accompanied by a loss of the normal structure of the placenta and degenerative manifestation at this level were observed. Moreover, we noted a striking alteration of the fetal face in 33-39% of experimental fetuses, called by us carnival fetuses. PMID:1079862
Tshibangu, K; Oosterwijck, K; Doumont-Meyvis, M
The effect of exposure to hypergravity on pregnant rat dams, pregnancy outcome and early neonatal development
NASA Astrophysics Data System (ADS)
We previously reported that hypergravity exposure affects food intake and mass gain during pregnancy. In the present study, we explored the hypothesis that changes in maternal body mass in hypergravity-exposed pregnant rat dams affect pregnancy outcome and early offspring development. Furthermore, we hypothesized that the changes observed at 1.5G will be magnified at higher gravity and by exposure during critical developmental periods. To test this hypothesis, we compared maternal body mass gain, food consumption, birth outcome and early offspring development between Sprague Dawley rat dams exposed to graded (1.5 1.75G) chronic hypergravity (HG) or rotation (rotational control, RC) on a 24-ft centrifuge for 22.5 h starting on gestational day (G) 10 with dams housed under identical conditions but not exposed to hypergravity (SC). We also compared maternal body mass, food consumption, birth outcome and early offspring development between rat dams exposed to 1.65G during different stages of pregnancy and nursing. Exposure to hypergravity resulted in transient loss in body mass and prolonged decrease in food consumption in HG dams, but the changes observed at 1.5G were not magnified at 1.65G or 1.75G. On the other hand RC dams gained more mass and consumed more food than SC dams. Exposure to hypergravity also affected pregnancy outcome as evidenced by decreased litter size, lowered neonatal mass at birth, and higher neonatal mortality; pregnancy outcome was not affected in RC dams. Neonatal changes evidenced by impaired righting response observed at 1.5G was magnified at higher gravity and was dependent on the period of hypergravity exposure. On the other hand, righting response was improved in RC neonates. Hypergravity exposure during early postpartum affected the food consumption of nursing mothers and affected early survival of their offspring. The changes observed in dams and neonates appear to be due to hypergravity exposure since animals exposed to the rotation during the same period are not affected. This study suggests that while pregnancy can proceed under altered gravity, exposure to hypergravity affects pregnant dams, pregnancy outcome and the developing fetus as well as nursing dams and neonates and raises an important question whether the mammalian system possess a gravisensing ability.
Ladd, B.; Nguon, K.; Sajdel-Sulkowska, E. M.
[Body weight and skeletal growth in female rats after ovariectomy].
The body weight gain and growth of tail and tibia were investigated in ovariectomized female rats to ascertain whether the increased skeletal growth after ovariectomy takes place at the same time as the increased body weight gain. Female rats were ovariectomized on the 30th day of age; half of them was killed on the 60th day of age and the other half was killed on the 130th day of age. The body weight and tail length were significantly higher in the ovariectomized females than in intact females from the 60th day of age (Figs. 1, 2). The ovariectomized animals had higher body weight gain and tail length increment, in comparison with intact animals, mainly between the 40th and 60th day of age (Tabs. I, II). After the 90th day of age the body weight gain and tail length increment were no longer significantly higher in ovariectomized animals than in intact animals, although the ovariectomized females maintained the significantly higher body weight and tail length till the end of the experiment (130th day of age). The length of tibia was larger in ovariectomized animals if compared with controls, on the 60th as well as on the 130th day of age. However, the rate of longitudinal growth of tibia, measured (by tetracycline method) between the 57th and 59th day and between the 127th and 129th day of age, was significantly higher in ovariectomized animals only in the first period of measurement (Tab. III).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8122344
Cíkos, S; Kuchár, S; Koppel, J
Disposition of orally administered 2,2-Bis(4-hydroxyphenyl)propane (Bisphenol A) in pregnant rats and the placental transfer to fetuses.
We studied the disposition of bisphenol A (BPA) in pregnant female F344/DuCrj(Fischer) rats and its placental transfer to fetuses after a single oral administration of 1 g/kg BPA dissolved in propylene glycol. BPA in maternal blood, liver, and kidney reached maximal concentrations (14.7, 171, and 36 microg/g) 20 min after the administration and gradually decreased. The levels were 2-5% of the maximum 6 hr after the administration. The maximal concentration of BPA in fetuses (9 microg/g) was also attained 20 min after the administration. BPA levels then gradually reduced in a similar manner to maternal blood. These results suggest that the absorption and distribution of BPA in maternal organs and fetuses are extremely rapid and that the placenta does not act as a barrier to BPA.
Takahashi, O; Oishi, S
Vulnerability to (+)-Methamphetamine Effects and the Relationship to Drug Disposition in Pregnant Rats during Chronic Infusion
Chronic (+)-methamphetamine (METH) use during pregnancy increases the health risk for both mother and fetus. To provide insights into these risks, the relationship between changes in METH disposition and METH-induced pharmacological effects were studied in Sprague-Dawley rat dams and litters. Timed-pregnant rats (n = 5–6) were given saline or METH (5.6–17.8 mg/kg/day) by continuous sc infusion from gestational day (GD) 7 (before organogenesis) until GD21 (0–2 days before delivery). By GD11, all rats in the 17.8-mg/kg/day group died or were sacrificed for humane reasons. There were significant (p < 0.05) dose- and gestational time-dependent decreases in maternal body weight in the 10- to 13.2-mg/kg/day groups, which slowly recovered to near normal by GD21. Continued METH dosing in the surviving groups did not affect the mean pups/litter weight at the end of the experiment on GD21. While maternal and fetal METH and (+)-amphetamine serum concentrations were similar on GD21, brain concentrations were significantly greater in the dams (p < 0.05). Importantly, brain-to-serum ratios in the dams were 9:1 and 3:1 in the pups. METH systemic clearance (ClS) in dams significantly (p < 0.05) decreased from 52 ± 14 ml/min/kg on GD10 to 28 ± 6 ml/min/kg on GD21 in all dose groups, indicating late-gestational stage reductions in METH ClS. Overall, these findings suggest that there were two periods of increased susceptibility for dams and fetuses during chronic METH treatment. First was the period after the start of METH dosing in which neuroadaptation and tolerance to METH occurs in the adult. The second was at the end of pregnancy when METH clearance was significantly reduced.
White, Sarah J.; Laurenzana, Elizabeth M.; Gentry, William Brooks; Hendrickson, Howard P.; Williams, David Keith; Ward, Keith W.; Owens, Samuel Michael
Expression of Endothelin 1 and Its Receptors in the Hypoxic Pregnant Rat1
Endothelin 1 (EDN1) plays a primary role in the pathophysiology of hypoxia-induced fetal growth restriction in the rat. In this study we evaluated the effects of chronic maternal hypoxia on the expression of endothelin and its receptors and on receptor binding activity in the uterus and placenta of the rat, in order to elucidate their roles in hypoxia-induced fetal growth restriction. Timed-pregnant Sprague-Dawley rats were maintained in either a normoxic or a normobaric hypoxic (12% O2) atmosphere from Gestational Days 18–21. Uterine and placental tissues collected on Gestational Day 21 were assayed for Edn1, Ednra, and Ednrb (endothelin receptors) mRNA expression by real-time quantitative RT-PCR, for localization of EDN1 and its receptors by immunohistochemistry, for EDNRA and EDNRB protein expression by Western blot, and for receptor binding activity by homologous competitive binding assays. EDN1 mRNA expression was significantly increased in the hypoxic placenta, but not in the uterus, compared with normoxic controls. Immunohistochemistry revealed increased EDN1 specifically in the labyrinth of the placenta. Receptor mRNA levels were not significantly affected by hypoxia, but EDNRA protein expression was significantly decreased specifically in the uterine placental beds. Receptor binding decreased significantly in response to hypoxia in all tissues investigated, compared with controls. These results suggest that chronic maternal hypoxia results in increased expression of EDN1 in the placenta but not in the uterus, and that reduced binding activity, rather than regulation of receptor expression, is a mechanism by which these tissues regulate the local hemodynamic response to increased endogenous placental EDN1 in the setting of hypoxia.
Thaete, Larry G.; Jilling, Tamas; Synowiec, Sylvia; Khan, Saira; Neerhof, Mark G.
Release of Zn from maternal tissues in pregnant rats deficient in Zn or Zn and Ca
Earlier studies have shown that diets that increase tissue catabolism reduce the teratogenic effects of Zn deficiency. The hypothesis that Zn may be released from body tissues when the metabolic state is altered was further tested. Nonpregnant Sprague Dawley females were injected with Zn-65; after equilibration, the two major pools of Zn, bone and muscle, had different specific activities (SA), muscle being much higher. Females were mated and fed diets adequate in Zn and Ca (C) or deficient in Zn (ZnD) or deficient in both Zn and Ca (ZnCaD). Calculations using weight loss in ZnD and ZnCaD rats, Zn content of maternal bone and muscle, and total fetal Zn at term indicated that in ZnCaD rats a relatively small amount of Zn from bone early in pregnancy was sufficient to prevent abnormal organogenesis, but most fetal Zn came from breakdown of maternal muscle in the last 3 days of pregnancy. Isotope data supported this conclusion. SA of Zn in ZnD fetuses was equal and high, indicating that most Zn came from the same maternal tissue. High muscle SA prior to mating, and increased SA in tibia and liver during pregnancy suggest that muscle provided Zn for other maternal tissues as well as fetuses. In contrast, SA in C fetuses was less than 30% of that of the D groups, consistent with the earlier hypothesis that most fetal Zn in C rats is accrued directly from the diet.
Hurley, L.S.; Masters, D.G.; Lonnerdal, B.; Keen, C.L.
Intrauterine growth restriction transiently delays alveolar formation and disrupts retinoic acid receptor expression in the lung of female rat pups
Background We showed that intrauterine growth restriction (IUGR) increases distal airspace wall thickness at birth (postnatal age 0; P0) in rat pups (saccular stage of lung development). However, that report did not assess whether the saccular phenotype persisted postnatally or occurred in males or females. Nor did that report identify a potential molecular pathway for the saccular phenotype at P0. We hypothesized that IUGR persistently delays alveolar formation and disrupts retinoic acid receptor (RAR) mRNA and protein levels in the lung of rat pups in postnatal age- and sex-specific manners. Methods IUGR was induced in pregnant rats by bilateral uterine artery ligation. Alveolar formation and expression of RAR?, ?, and ? were quantified at P0, P6 (alveolar stage), and P21 (postalveolarization). Results IUGR increased distal airspace wall thickness in female pups at P0 only. IUGR did not affect male pups at any age. IUGR transiently increased lung RAR? protein abundance, which inhibits alveolar formation, at P0 in female pups. Serum retinol concentration was normal at all ages. Conclusions IUGR alone is not sufficient to persistently delay postnatal alveolar formation or disrupt expression RARs. We speculate that for IUGR to delay alveolar formation postnatally, a second insult is necessary.
Yang, Yan; Fitzhugh, Melanie; Metcalfe, Drew; Oman, Jake; Hale, Merica; Dong, Li; Wang, Zheng-Ming; Yu, Xing; Callaway, Christopher W.; O'Brien, Elizabeth; McKnight, Robert A.; Lane, Robert H.; Albertine, Kurt H.
High Folic Acid Intake during Pregnancy Lowers Body Weight and Reduces Femoral Area and Strength in Female Rat Offspring
Rats fed gestational diets high in multivitamin or folate produce offspring of altered phenotypes. We hypothesized that female rat offspring born to dams fed a gestational diet high in folic acid (HFol) have compromised bone health and that feeding the offspring the same HFol diet attenuates these effects. Pregnant rats were fed diets with either recommended folic acid (RFol) or 10-fold higher folic acid (HFol) amounts. Female offspring were weaned to either the RFol or HFol diet for 17 weeks. HFol maternal diet resulted in lower offspring body weights (6%, P = 0.03) and, after adjusting for body weight and femoral length, smaller femoral area (2%, P = 0.03), compared to control diet. After adjustments, HFol pup diet resulted in lower mineral content (7%, P = 0.01) and density (4%, P = 0.002) of lumbar vertebra 4 without differences in strength. An interaction between folate content of the dam and pup diets revealed that a mismatch resulted in lower femoral peak load strength (P = 0.01) and stiffness (P = 0.002). However, the match in folate content failed to prevent lower weight gain. In conclusion, HFol diets fed to rat dams and their offspring affect area and strength of femurs and mineral quantity but not strength of lumbar vertebrae in the offspring.
Huot, Pedro S. P.; Dodington, David W.; Mollard, Rebecca C.; Reza-Lopez, Sandra A.; Sanchez-Hernandez, Diana; Cho, Clara E.; Kuk, Justin; Ward, Wendy E.; Anderson, G. Harvey
Pivalate lowers litter sizes and weights in female rats independent of its effect on carnitine status
The present study investigated whether treatment of female rats with pivalate affects their reproductive function. Therefore, two experiments with female rats were performed. The first experiment included two groups of rats which received drinking water without (control) or with 20mmol pivalate\\/L. The second experiment included a control group (which received drinking water without pivalate and a diet without added carnitine)
Jane Doberenz; Frank Hirche; Uta Keller; Klaus Eder
Are endogenous sex hormones related to DNA damage in paradoxically sleep-deprived female rats?
The aim of this investigation was to evaluate overall DNA damage induced by experimental paradoxical sleep deprivation (PSD) in estrous-cycling and ovariectomized female rats to examine possible hormonal involvement during DNA damage. Intact rats in different phases of the estrous cycle (proestrus, estrus, and diestrus) or ovariectomized female Wistar rats were subjected to PSD by the single platform technique for
Monica L. Andersen; Daniel A. Ribeiro; Tathiana A. Alvarenga; Andressa Silva; Paula Araujo; Adriano Zager; Neuli M. Tenorio; Sergio Tufik
Delayed alternation in adolescent and adult male and female rats.
The prefrontal cortex continues to develop throughout adolescence in several species, and our laboratory has demonstrated that during adolescence there is a decrease in neurons in the rat medial prefrontal cortex (mPFC). A PFC-dependent task, the delayed alternation task, was used in the present study to examine the function of the mPFC while it is still maturing in rats of both sexes. A deficit was found in adolescents when compared to adults during 15- and 60-s delays but not at other delays (5, 10, 30, and 90 s). Furthermore, adolescents committed more perseverative errors. No significant sex differences occurred at any delay for either age group; however, in the no delay training sessions, adolescent males reached criterion faster than females. These results indicate that performance on a mPFC-dependent task improves between adolescence and adulthood. PMID:21432847
Koss, Wendy A; Franklin, Andrew D; Juraska, Janice M
Thermoregulatory ability of female rats during pregnancy and lactation.
Thermoregulatory ability of female rats was examined before pregnancy, during gestation, and during lactation. Thermoregulatory pattern, colonic temperature, evaporative water loss, and survival time were monitored during terminal heating (39.5 +/- 0.9 degrees C) designed to allow prolonged survival (3-4 h) with a sustained thermoregulatory effort. Results confirmed our previously reported observation of decreased thermoregulatory ability in lactating dams, with evidence suggesting thermoregulatory impairment during late gestation. Lactating dams displayed a type III thermoregulatory pattern, and established a rate of evaporative water loss effective for thermostasis at an elevated colonic temperature. However, survival time was significantly decreased compared to nonreproducing females. In contrast, prior heat acclimation tended to increase the survival time of lactating dams. It was concluded that the reduction in thermoregulatory ability observed in lactating dams was related to their inability to maintain a rate of evaporative water loss effective for thermostasis at an elevated colonic temperature. PMID:7192056
Knecht, E A; Toraason, M A; Wright, G L
Effect of pregnandiol on caffeine metabolism in female rats
Summary Three groups of six 5-week-old Sprague Dawley female rats received i.p. injections of pregnandiol, 1.25, 2.50 or 5 mg\\/kg,\\u000a respectively, in triolein daily for 7 days. Caffeine metabolism was studied in liver slices on day 8 by HPLC. Only primary\\u000a metabolites were formed. N-1 demethylation was the most important pathway (theobromine represented 51% of total dimethylxanthines).\\u000a Unlike in human in
T. Bienvenu; G. Pons; E. Rey; G. Thiroux; G. Olive
Appearance of circulating and tissue /sup 14/C-lipids after oral /sup 14/C-tripalmitate administration in the late pregnant rat
Studies were performed to determine whether and/or how dietary lipids participate in maternal hypertriglyceridemia during late gestation in the rat. After oral administration of glycerol-tri(1-14C)-palmitate, total radioactivity in plasma increased more rapidly in 20-day pregnant rats than in either 19-day pregnant rats or virgin controls. At the peak of plasma radioactivity, four hours after the tracer was administered, most of the plasma label corresponded to 14C-lipids in triglyceride-rich lipoproteins (d less than 1.006), and when expressed per micromol of triglyceride, values were higher in pregnant than in virgin rats. The difference was less after 24 hours, although at this time the level of 14C-lipids in d less than 1.006 lipoproteins was still higher in 20-day pregnant rats than in virgins. Tissue 14C-lipids, as expressed per gram of fresh weight, were similar in pregnant and virgin rats, but the values in mammary glands were much higher in the former group. Estimated recovery of administered radioactivity four hours after tracer in total white adipose tissue, mammary glands, and plasma lipids was higher in pregnant than in virgin rats. No difference was found between 20-day pregnant and virgin rats either in the label retained in the gastrointestinal tract or in that exhaled as 14C-CO2 during the first four hours following oral administration of 14C-tripalmitate. These findings plus the known maternal hyperphagia, indicate that in the rat at late pregnancy triglyceride intestinal absorption is unchanged or even enhanced and that dietary lipids actively contribute to both maternal hypertriglyceridemia and lipid uptake by the mammary gland.
Argiles, J.; Herrera, E.
Prior access to a sweet is more protective against cocaine self-administration in female rats than male rats
It is well established that female rats are more sensitive than male rats to the reinforcing effects of cocaine (Lynch, 2008 for review). We hypothesized that greater preference for cocaine would support greater avoidance of a cocaine-paired taste cue in female vs. male rats. Moreover, at least in male rats, greater avoidance of the taste cue is associated with greater cocaine self-administration (Grigson & Twining, 2002). Thus, we anticipated that female rats would not only demonstrate greater avoidance of the drug-paired taste cue, but greater drug-taking as well. We tested these hypotheses by examining avoidance of a saccharin cue in male and female rats following several pairings with self-administered saline or cocaine (0.16, 0.33, or 0.66 mg/infusion). Contrary to expectations, the results showed that female rats exhibited less avoidance of the cocaine-associated saccharin cue than male rats and self-administered less, rather than more, cocaine, Thus, while female rats reportedly take more drug than male rats when the drug is presented in the absence of an alternative reward, they take less drug than male rats when the opportunity to self-administer cocaine is preceded by access to a palatable sweet. Females, then, may not simply be more sensitive to the rewarding properties of drug, but also to the reinforcing properties of natural rewards and this increase in sensitivity to sweets may serve to protect against drug-taking behavior.
Cason, Angie M.; Grigson, Patricia S.
Prior access to a sweet is more protective against cocaine self-administration in female rats than in male rats.
It is well established that female rats are more sensitive than male rats to the reinforcing effects of cocaine (Lynch, 2008 [42] for review). We hypothesized that greater preference for cocaine would support greater avoidance of a cocaine-paired taste cue in female vs. male rats. Moreover, at least in male rats, greater avoidance of the taste cue is associated with greater cocaine self-administration (Grigson and Twining, 2002 [3]). Thus, we anticipated that female rats would not only demonstrate greater avoidance of the drug-paired taste cue, but greater drug-taking as well. We tested these hypotheses by examining avoidance of a saccharin cue in male and female rats following several pairings with self-administered saline or cocaine (0.16, 0.33, or 0.66 mg/infusion). Contrary to expectations, the results showed that female rats exhibited less avoidance of the cocaine-associated saccharin cue than male rats and self-administered less, rather than more, cocaine, Thus, while female rats reportedly take more drug than male rats when the drug is presented in the absence of an alternative reward, they take less drug than male rats when the opportunity to self-administer cocaine is preceded by access to a palatable sweet. Females, then, may not simply be more sensitive to the rewarding properties of drug, but also to the reinforcing properties of natural rewards and this increase in sensitivity to sweets may serve to protect against drug-taking behavior. PMID:23474135
Cason, Angie M; Grigson, Patricia S
Toxicological evaluation and metal bioavailability in pregnant rats following exposure to clay minerals in the diet.
Silicate clays are frequently added to animal feeds to bind and reduce the bioavailability of mycotoxins in the gastrointestinal tract. However, the bioavailability of trace metals in these clay feed additives has not been thoroughly investigated. Clays that act nonselectively may interact with nutrients, minerals, and other feedborne chemicals to pose significant hidden risks. In this study, a calcium montmorillonite clay (Novasil Plus, NSP) commonly used as an enterosorbent for aflatoxins and a sodium montmorillonite clay (Swy-2) (Source Clay Minerals Repository, Columbia, MO) were examined. Clays were supplemented in the balanced diet of Sprague-Dawley rats during pregnancy at a level of 2% (w/w). Evaluations of toxicity were performed on gestation d 16 and included maternal body weights, maternal feed intakes, litter weights, and embryonic resorptions. Liver, kidneys, tibia, brain, uterus, pooled placentas, and pooled embryonic mass were collected and weighed. Tissues were lyophilized and neutron activation analysis (NAA) was performed. Elements considered by NAA included Al, Ba, Br, Ca, Ce, Co, Cr, Cs, Cu, Dy, Eu, Fe, Hf, K, La, Lu, Mg, Mn, Na, Nd, Ni, Rb, S, Sb, Sc, Se, Sm, Sr, Ta, Tb, Te, Th, Ti, Tl, U, V, Yb, Zn, and Zr. Inductively coupled plasma-mass spectroscopy further confirmed that Al was below detection limits (<0.5 ppm) in the brain. Animals supplemented with either NSP or Swy-2 were similar to controls with respect to toxicity evaluations and metal analysis, with the exception of decreased brain Rb following clay supplementation. Overall, the results of this study suggest that neither NSP nor Swy-2, at relatively high dietary concentrations, influences mineral uptake or utilization in the pregnant rat. PMID:15205041
Wiles, Melinda; Huebner, Henry; Afriyie-Gyawu, Evans; Taylor, Robert; Bratton, Gerald; Phillips, Timothy
Toxicokinetic assessment of methylphenidate (Ritalin) enantiomers in pregnant rats and rabbits.
Ritalin or methylphenidate (MPH) is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. The present report describes the determination of plasma concentrations of D-threo- and L-threo-enantiomers of MPH in toxicokinetic (TK) studies in pregnant Wistar Hannover rats and New Zealand white rabbits following repeated daily oral dosing of D,L-MPH (racemate). A previously reported chiral liquid chromatography tandem mass spectrometric (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.09 ng/mL was utilized. Oral (gavage) doses of 7, 25 and 75 mg/kg/day of racemic MPH were selected for the rat study. An over-proportional increase in exposure was observed with increasing doses of MPH racemate, the effect being more profound with the D- than the L-enantiomer. In contrast, Cmax values of both enantiomers were approximately proportional to the dose. Oral (gavage) doses of 20, 60 and 200 mg/kg were selected for the rabbit study. In general, for the D-isomer, an over-proportional increase in exposure was observed with increasing doses of MPH racemate. Conversely, for the L-isomer, a slight under-proportionality was detected in exposure with increasing doses of D,L-MPH. For mean Cmax, while L-isomer exhibited dose proportionality with increasing doses of MPH racemate, the D-isomer appeared to be over-proportional. Herein, the experimental design and observed TK parameters in each study are presented. PMID:15236434
Bakhtiar, Ray; Tse, Francis L S
Magnesium sulphate treatment decreases blood-brain barrier permeability during acute hypertension in pregnant rats.
Eclampsia is associated with increased blood-brain barrier (BBB) permeability and formation of cerebral oedema. Magnesium sulphate is used to treat eclampsia despite an unclear mechanism of action. This study was to determine the effect of magnesium sulphate on in vivo BBB permeability and formation of cerebral oedema during acute hypertension and on brain aquaporin-4 (AQP4) protein expression. An in vivo model of hypertensive encephalopathy was used in late-pregnant (LP) rats following magnesium sulphate treatment, 270 mg kg(-1) i.p. injection every 4 h for 24 h. Permeability of the BBB was determined by in situ brain perfusion of Evan's Blue (EB) and sodium fluorescein (NaFl), and dye clearance determined by fluorescence spectrophotometry. Cerebral oedema was determined following acute hypertension by measuring brain water content. The effect of magnesium treatment on AQP4 expression was determined by Western blot analysis. Acute hypertension with autoregulatory breakthrough increased BBB permeability to EB in both brain regions studied (P < 0.05). Magnesium attenuated BBB permeability to EB during acute hypertension by 41% in the posterior cerebrum (P < 0.05) but had no effect in the anterior cerebrum (P > 0.05). Treatment with magnesium did not change NaFl permeability, cerebral oedema formation or AQP4 expression. In summary, BBB permeability to Evan's Blue was increased by acute hypertension in LP rats, and this was attenuated by treatment with magnesium sulphate. The greatest effect on BBB permeability to EB was in the posterior cerebrum, an area particularly susceptible to oedema formation during eclampsia. PMID:17933863
Euser, Anna G; Bullinger, Lisa; Cipolla, Marilyn J
Functional expression of purinergic P2X7 receptors in pregnant rat myometrium.
ATP has been reported to enhance the membrane conductance of myometrial cells and uterine contractility. Purinergic P2 receptor expression has been reported in the myometrium, using molecular biology, but the functional identity of the receptor subtype has not been determined. In this study, ATP-induced currents were recorded and characterized in single myometrial cells from pregnant rats using whole cell patch clamping. Extracellular ATP was applied in the range of 10 muM-1 mM and induced currents with an EC(50) of 74 muM, with no desensitization, time dependency, or voltage dependency. The currents induced carried multiple monovalent cations, with conductances ranked as K(+) > Cs(+) > Li(+) > Na(+). They were activated by P2X receptor agonists, with their effectiveness ranked as 2',3'-O-(4-benzoylbenzoyl)-ATP > ATP > alphabeta-methylene-ATP > 2-methylthio ATP > or = UTP > or = GTP > ADP. These currents were blocked by the selective P2X7 receptor antagonist 3-[5-(2,3-dichlorophenyl)-1 H-tetrazol-1-yl]methyl pyridine (A-438079). We therefore concluded that ATP-induced currents in rat myometrial cells crossed cell membranes via P2X7 receptors. We further showed that the ATP-induced currents were blocked by extracellular Mg(2+) (IC(50) = 0.26 mM). Clinically, administering extracellular Mg(2+) is known to inhibit uterine contraction. It therefore seems likely that uterine contraction may be induced by raised extracellular ATP and suppressed via Mg(2+) inhibiting P2X7 receptors. Further research is needed into the P2X7 receptor as a therapeutic target in abnormal uterine contraction, as a possible treatment for premature labor. PMID:20071613
Miyoshi, Hiroshi; Yamaoka, Kaoru; Urabe, Satoshi; Kodama, Miho; Kudo, Yoshiki
Altered Endothelin Receptor Binding in Response to Nitric Oxide Synthase Inhibition in the Pregnant Rat
The authors evaluate the expression of endothelin-1 (ET-1) and its receptors in the uterus and placenta during maternal nitric oxide synthase (NOS) inhibition. Timed-pregnant rats received L-NAME (2.5 mg/kg/h) or saline from day 14 to 21 of gestation. Uterine and placental tissues collected on day 21 were assayed for preproET-1, ETA, and ETB mRNA expression; localization and expression of ET-1 and receptor proteins; and receptor activity. NOS inhibition did not affect preproET-1 mRNA expression in the placenta or uterus. ETA expression decreased in the uterine free wall, but no other changes in receptor mRNA expression were observed in the uterus or placenta. ET-1 and receptor proteins were unchanged. Placental ETA and ETB receptor binding decreased. Uterine ETA receptor binding decreased in the placental bed. ET-1, a prominent mediator during NOS inhibition, is not of uterine or placental origin. Reduced receptor binding activity is the primary means by which these tissues regulate their response to ET-1 in the setting of NOS inhibition.
Neerhof, Mark G.; Jilling, Tamas; Synowiec, Sylvia; Khan, Saira; Thaete, Larry G.
Clinostat rotation induces apoptosis in luteal cells of the pregnant rat
NASA Technical Reports Server (NTRS)
Recent studies have shown that microgravity induces changes at the cellular level, including apoptosis. However, it is unknown whether microgravity affects luteal cell function. This study was performed to assess whether microgravity conditions generated by clinostat rotation induce apoptosis and affect steroidogenesis by luteal cells. Luteal cells isolated from the corpora lutea of Day 8 pregnant rats were placed in equal numbers in slide flasks (chamber slides). One slide flask was placed in the clinostat and the other served as a stationary control. At 48 h in the clinostat, whereas the levels of progesterone and total cellular protein decreased, the number of shrunken cells increased. To determine whether apoptosis occurred in shrunken cells, Comet and TUNEL assays were performed. At 48 h, the percentage of apoptotic cells in the clinostat increased compared with that in the control. To investigate how the microgravity conditions induce apoptosis, the active mitochondria in luteal cells were detected with JC-1 dye. Cells in the control consisted of many active mitochondria, which were evenly distributed throughout the cell. In contrast, cells in the clinostat displayed fewer active mitochondria, which were distributed either to the outer edge of the cell or around the nucleus. These results suggest that mitochondrial dysfunction induced by clinostat rotation could lead to apoptosis in luteal cells and suppression of progesterone production.
Yang, Hyunwon; Bhat, Ganapathy K.; Sridaran, Rajagopala
Re-Adaptation to 1-G of Pregnant Rats Following Exposure to Spaceflight or Centrifugation
NASA Technical Reports Server (NTRS)
Late-pregnant rat dams were flown on a 9-day Space Shuttle mission or exposed to 1.5, 1.75 or 2-g centrifugation and compared with 1 .O-g vivarium controls. Exposure to altered gravity began on the 11th day and recovery occurred on the 20th day of the dams' 22-day pregnancy. In the 1 st experiment, comparisons were made between Flight (FLT), Synchronous (SYN; identically-housed) and Vivarium (VIV) controls. In the 2nd experiment, comparisons were made between dams centrifuged at 2-G, 1.75-G, 1.5-G, Rotational controls (1.08-G) or Stationary controls (1 G). Within three hours of recovery from either spaceflight or centrifugation, the dams' locomotor behavior was videotaped for 2 min. FLT dams showed dramatically reduced movement relative to both SYN and VIV control conditions, with significantly greater amounts of locomotor activity observed in SYN as compared to VIV dams. Significantly greater locomotor activity was observed in SYN as compared to VIV controls. In the second experiment, no differences were observed between dams exposed either 1, 1.5, 1.75, or 2-G. In both studies, the dams showed similar patterns of hindlimb rearing. Together, these findings provide quantitative evidence for decreased locomotor activity during re-adaptation to 1-g following spaceflight, but not centrifugation.
Johnson, K. E.; Ronca, A. E.; Alberts, J. R.
Uptake of marker proteins by glycoprotein-containing cells of the pregnant rat uterus and placenta.
A study was made of cells in the pregnant rat uterus and placenta known to contain glycoprotein inclusions to investigate their ability to endocytose marker proteins (fluorescein conjugated serum and horseradish peroxidase) injected into the maternal circulation. The visceral endoderm showed marked uptake of both proteins, though in later pregnancy this was restricted to the area of yolk sac adjacent to the chorio-allantoic placenta. The intracellular distribution of the endocytosed marker proteins resembled that of the glycoprotein inclusions. In the earlier stages some of the giant cell inclusions contained glycoprotein, some showed staining with the Dunn-Thompson technique for haemoglobin, and some showed peroxidase activity. There was endocytosis of both marker proteins by giant cells, and apparently this occurred independently of ingestion of red blood cells. Uptake by the giant cells persisted to a later stage in the area round the margin of the chorio-allantoic placenta than in the other giant cells. Endocytosis occurred in the labyrinthine trophoblast, and the glycoprotein inclusions found in this situation may represent material being transmitted or digested. The glycoprotein-containing granulated metrial gland cells showed no evidence of endocytotic activity, but there was uptake of both marker proteins by the associated stromal cells. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Figs. 12-13 Fig. 14 Fig. 15 Fig. 16 Fig. 17 Fig. 18 Fig. 19
Sharma, R; Peel, S
Abolition of EndOrgan Damage by Antiandrogen Treatment in Female Hypertensive Transgenic Rats
We aimed at studying the role of androgens in the development of cardiovascular pathology in hypertensive female rats. Female TGR(mREN2)27 rats harboring the mouse Ren-2 renin gene were treated with Flutamide (specific antagonist of the androgen receptor, 30 mg\\/kg per day) starting at 4 weeks of age. Flutamide treatment significantly attenuated the development of hypertension in female rats (systolic blood
Ovidiu Baltatu; Cécile Cayla; Radu Iliescu; Dmitrii Andreev; Michael Bader
Effects of Tribulus terrestris on endocrine sensitive organs in male and female Wistar rats
Aim of the studyInvestigate the possible effects of Tribulus terrestris (TT) on endocrine sensitive organs in intact and castrated male rats as well as in a post-menopausal rat model using ovariectomized females.
Anderson J. Martino-Andrade; Rosana N. Morais; Katherinne M. Spercoski; Stefani C. Rossi; Marina F. Vechi; Munisa Golin; Natália F. Lombardi; Cláudio S. Greca; Paulo R. Dalsenter
Effects of methyl-deficient diets on methionine and homocysteine metabolism in the pregnant rat.
Although the importance of methyl metabolism in fetal development is well recognized, there is limited information on the dynamics of methionine flow through maternal and fetal tissues and on how this is related to circulating total homocysteine concentrations. Rates of homocysteine remethylation in maternal and fetal tissues on days 11, 19, and 21 of gestation were measured in pregnant rats fed diets with limiting or surplus amounts of folic acid and choline at two levels of methionine and then infused with L-[1-(13)C,(2)H(3)-methyl]methionine. The rate of homocysteine remethylation was highest in maternal liver and declined as gestation progressed. Diets deficient in folic acid and choline reduced the production of methionine from homocysteine in maternal liver only in the animals fed a methionine-limited diet. Throughout gestation, the pancreas exported homocysteine for methylation within other tissues. Little or no methionine cycle activity was detected in the placenta at days 19 and 21 of gestation, but, during this period, fetal tissues, especially the liver, synthesized methionine from homocysteine. Greater enrichment of homocysteine in maternal plasma than placenta, even in animals fed the most-deficient diets, shows that the placenta did not contribute homocysteine to maternal plasma. Methionine synthesis from homocysteine in fetal tissues was maintained or increased when the dams were fed folate- and choline-deficient methionine-restricted diets. This study shows that methyl-deficient diets decrease the remethylation of homocysteine within maternal tissues but that these rates are protected to some extent within fetal tissues. PMID:22454289
Wilson, Fiona A; Holtrop, Grietje; Calder, A Graham; Anderson, Susan E; Lobley, Gerald E; Rees, William D
Repeated ethanol exposure affects the acquisition of spatial memory in adolescent female rats.
Ethanol has been reported to disrupt spatial learning and memory in adolescent male rats. The present study was undertaken to determine the effects of ethanol on the acquisition of spatial memory in adolescent female rats. Adolescent female rats were subjected to repeated ethanol or saline treatments, and spatial learning was tested in the Morris water maze. For comparison, adult female rats were subjected to similar ethanol treatment and behavioral assessments as for adolescent rats. Ethanol-treated adolescent rats took longer and swam greater distances to find the hidden platform than saline controls. In the probe trial, ethanol-treated adolescent rats showed a trend towards reduced time spent in the target quadrant, and made significantly fewer target location crossings than saline-treated controls. Adult saline-treated control rats did not learn the spatial memory task as well as the adolescent saline-treated rats. Although ethanol in adult rats increased both latency and swim distance to find the platform, in the probe trial there was no difference between ethanol-treated adult rats and age-matched saline controls. Ethanol did not alter swim speed or performance in the cued visual task at either age. Together, these data suggest that ethanol specifically impairs the acquisition of spatial memory in adolescent female rats. Since adult females did not learn the task, ethanol-induced alterations in water maze performance may not reflect true learning and memory dysfunction. PMID:19463705
Sircar, Ratna; Basak, Ashim K; Sircar, Debashish
Juvenile male rats display lower cortical metabolic capacity than females
The juvenile brain undergoes marked maturational changes accompanied by major sex hormone changes. In particular, sex differences in neural substrates could underlie male-specific dysfunction in behavioral responses related to the prefrontal cortex. Sex differences in regional metabolic capacity of the cerebral cortex were investigated in juvenile Sprague-Dawley rats. At 6 weeks of age the brains were processed for quantitative histochemistry of cytochrome oxidase, a rate limiting enzyme in cellular respiration, which is an index of brain metabolic capacity. Quantitative image analysis revealed a main effect of sex with males displaying lower regional metabolic capacity than females in the dorsolateral and orbital prefrontal cortex and in the posterior parietal cortex. In addition, males separated for 6 hours/day from their mothers as pups showed greater ambulatory behavior in the novel open field and higher metabolism in the posterior parietal cortex relative to males separated for 15 min/day. This is the first study to show sex differences in brain metabolic capacity in regions such as the prefrontal cortex that may be hypometabolic in juvenile males relative to females.
Spivey, Jaclyn M.; Colorado, Rene A.; Conejo-Jimenez, Nelida; Gonzalez-Pardo, Hector; Gonzalez-Lima, F.
Phenotypic plasticity in female naked mole-rats after removal from reproductive suppression.
Naked mole-rats are fossorial African rodents that live in large, eusocial groups. Adult subordinate female mole-rats are reproductively suppressed by the dominant breeding female in their colonies. As a result, subordinate females remain reproductively quiescent for their entire lives unless they are removed from the suppressive presence of the dominant female. This makes subordinate female mole-rats a tractable model for studying phenotypic plasticity. We measured skeletal growth of subordinate, suppressed females as they changed reproductive status. After housing subordinate female mole-rats separately from their home colonies, these animals experienced a growth surge that dramatically increased their body mass and length. After removal from reproductive suppression, females showed an 82% increase in body mass and a 37% increase in the length of their lumbar spines. The lumbar vertebrae were the only skeletal structures that exhibited this puberty-like growth. After colony separation, body mass and lumbar vertebrae growth rates peaked and remained elevated for several weeks before returning to control levels--suggestive of a puberty-like 'growth spurt'. Although previous studies have characterized pregnancy-induced lumbar spine elongation in female mole-rats, we demonstrate a significant change in the body morphology of female mole-rats after removal from reproductive suppression but before the first pregnancy. PMID:18055624
Dengler-Crish, Christine M; Catania, Kenneth C
Ketamine administered to pregnant rats in the second trimester causes long-lasting behavioral disorders in offspring.
Commonly used anesthetic agents, e.g. ketamine, may be neurotoxic to the developing brain but there has been little attention to the neurobehavioral consequences for offspring when used for maternal anesthesia. We hypothesize that treatment of pregnant rats with ketamine during the second trimester would affect brain development of the offspring. Pregnant rats on gestational day 14, about equal to midtrimester pregnancy in humans, received a sedative dose of ketamine intravenously for 2h. Brain hippocampal morphology of their pups at postnatal days 0 (P0) and P30 was examined by Nissl-staining and the characteristics of dendrites were determined using the Golgi-Cox staining, while cell proliferation in subventricular zone (SVZ) and dentate gyrus (DG) was labeled with bromodeoxyuridine (BrdU). Their neurobehavioral functions were tested at P25-30 after which the NR1 and NR2 subunits of N-methyl-d-aspartate (NMDA) receptor, brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD-95) in the hippocampus were analyzed by western blot. When pregnant rats were exposed to ketamine, there was neuronal loss, pyramidal neuronal abnormality and reduced cell proliferation in the hippocampus of offspring. These morphological abnormalities were associated with depression- and anxiety-like behaviors, and impaired memory up to young adult age. The treatment further caused NR2A receptor subunit up-regulation and NR2B receptor subunit, BDNF and PSD-95 down-regulation. These data suggest that maternal anesthesia with ketamine during the fetal brain development period can cause fetal brain damage and subsequent neurobehavioral abnormality, which is likely associated with the imbalanced expression of NMDA receptor subunits. PMID:24780497
Zhao, Tianyun; Li, Yuantao; Wei, Wei; Savage, Sinead; Zhou, Libing; Ma, Daqing
Male and female Long-Evans rats were treated with epichlorohydrin (ECH) by oral gavage (males: 12.5, 25, and 50 mg/kg/day; females: 25, 50, and 100 mg/kg/day) for 21 and 14 days respectively, prior to mating trials with untreated animals. Treated females were further dosed until ...
Increased Activity of cGMP-Specific Phosphodiesterase (PDE5) Contributes to Resistance to Atrial Natriuretic Peptide Natriuresis in the Pregnant Rat
Increased cGMP-specific phosphodiesterase (PDE5) activity in renal inner medullary collecting duct (IMCD) cells contributes to resistance to atrial natriuretic peptide (ANP) and the excessive sodium retention seen in experimental nephrotic syndrome and liver cirrhosis. Normal pregnancy is also accompanied by sodium retention and plasma volume expansion, and pregnant rats are resistant to the natriuretic action of ANP. The authors investigated a possible role of increased renal PDE5 activity in the physiologic sodium retention of normal rat pregnancy. The natriuresis and increased urinary cGMP excretion (UcGMPV) evoked by acute volume expansion (a measure of renal responsiveness to endogeneous ANP) was blunted in 16-d pregnant versus virgin rats, despite equivalent increases in circulating ANP in pregnants and virgins. The ANP-dependent cGMP accumulation in isolated IMCD cells from pregnants was blunted versus virgins and restored by the PDE5-selective antagonist DMPPO (10?7 mol/L). PDE5 activity in vitro and PDE5 protein abundance in IMCD were greater in pregnants. Four days postpartum, volume expansion natriuresis, UcGMPV, and PDE5 protein levels in IMCD cell homogenates had returned to virgin values. These results demonstrate that normal rat pregnancy leads to in vivo and in vitro renal resistance to ANP, in association with heightened activity of the cGMP-specific PDE5 in IMCD. This may contribute to the physiologic sodium retention of normal pregnancy.
The impact of dose rate on ethylene glycol developmental toxicity and pharmacokinetics in pregnant CD rats.
High-dose bolus exposure of rats to ethylene glycol (EG) causes developmental toxicity mediated by a metabolite, glycolic acid (GA), whose levels increase disproportionately when its metabolism is saturated. However, low-level exposures that do not saturate GA metabolism have a low potential for developmental effects. Toward the goal of developing EG risk assessments based on internal dose metrics, this study examined the differences between fast (bolus) and slow (continuous infusion) dose-rate exposures to EG on developmental outcome and pharmacokinetics. Time-mated female CD rats received sc bolus injections of 0, 1000, or 2000 mg/kg/day of EG on gestation day (GD) 6-15 once daily, whereas three corresponding groups were given the same daily doses as an infusion administered continuously from GD 6-15 via an sc implantable pump. In the sc bolus groups, increases in 11 fetal malformations (major defects) and 12 variations (minor alterations) were seen at the 2000 mg/kg/day dose level, whereas increases in 2 malformations and 2 variations occurred at 1000 mg/kg/day. In contrast, equivalent daily doses of EG given slowly via infusion did not cause any developmental effects. A pharmacokinetics time course was then conducted to compare GD 11-12 kinetics from oral bolus (gavage) exposure versus sc infusion of EG. Although dose rate had a modest impact (8- to 11-fold difference) on peak EG levels, peak levels of GA in maternal blood, kidney, embryo, and exocoelomic fluid were 59, 100, 49, and 56 times higher, respectively, following gavage versus the same dose given by infusion. These data illustrate how high-dose bolus exposure to EG causes a dramatic shift to nonlinear GA kinetics, an event which is highly unlikely to occur following exposures to humans associated with consumer and worker uses. PMID:20952502
Carney, Edward W; Tornesi, Belen; Liberacki, Ashley B; Markham, Daniel A; Weitz, Karl K; Luders, Teressa M; Studniski, Kristine G; Blessing, John C; Gies, Richard A; Corley, Richard A
A Novel Telometric Metric for In-Situ Measurement of Intrauterine Pressure (IUP) in Pregnant and Parturient Rats
NASA Technical Reports Server (NTRS)
During labor and birth, considerable forces exerted on fetuses help instigate certain adaptive postpartum responses (viz., breathing and suckling). To make precise, reliable measures of the forces experienced by rat fetuses during parturition, we developed a novel method for measuring intrauterine pressure (IUP) in late pregnant rats. A small (1.25 x 4cm) telemetric blood pressure sensor is fitted within a fluid-filled balloon, similar in size to a full term rat fetus. The balloon is surgically implanted in the uterus on Gestational Day 19 of the rats' 22-day pregnancy. During birth, dams are able to deliver their pups and the balloon. IUP arsenals are recorded during labor (G22 or 23) and birth. Data derived from a group of implanted rats indicated that pressures on the balloon increased across the period of birth, reaching 18 mmHg during labor, 25 mmHg during pup births and 39 mmHg just prior to delivery of the balloon. These data are within the range reported for conventional IUP measurement techniques. Dams are simultaneously videotaped, enabling us to analyze behavioral expressions of labor contractions and to integrate in-situ and behavioral findings.
Baer, Lisa A.; LaFramboise, M. N.; Hills, E. M.; Daly, M. E.; Mills, N. A.; Wade, C. E.; Ronca, A. E.; Dalton, Bonnie (Technical Monitor)
Female rats are more susceptible to central nervous system oxygen toxicity than male rats.
Abstract Tonic-clonic seizures typify central nervous system oxygen toxicity (CNS-OT) in humans and animals exposed to high levels of oxygen, as are encountered during scuba diving. We previously demonstrated that high doses of pseudoephedrine (PSE) decrease the latency to seizure (LS) for CNS-OT in young male rats. This study investigated whether female rats respond similarly to PSE and hyperbaric oxygen (HBO). We implanted 60 virgin stock (VS) and 54 former breeder (FB) female rats with radio-telemetry devices that measured brain electrical activity. One week later, rats were gavaged with saline or PSE in saline (40, 80, 120, 160, or 320 mg/kg) before diving to five atmospheres absolute in 100% oxygen. The time between reaching maximum pressure and exhibiting seizure was LS. Vaginal smears identified estrus cycle phase. PSE did not decrease LS for VS or FB, primarily because they exhibited low LS for all conditions tested. VS had shorter LS than males at 0, 40, and 80 mg/kg (-42, -49, and -57%, respectively). FB also had shorter LS than males at 0, 40, and 80 mg/kg (-60, -86, and -73%, respectively). FB were older than VS (286 ± 10 days vs. 128 ± 5 days) and weighed more than VS (299 ± 2.7 g vs. 272 ± 2.1 g). Males tested were younger (88 ± 2 days), heavier (340 ± 4.5 g), and gained more weight postoperatively (7.2 ± 1.6 g) than either VS (-0.4 ± 1.5 g) or FB (-1.6 ± 1.5 g); however, LS correlated poorly with age, body mass, change in body mass, and estrus cycle phase. We hypothesize that differences in sex hormones underlie females' higher susceptibility to CNS-OT than males. PMID:24771690
Held, Heather E; Pilla, Raffaele; Ciarlone, Geoffrey E; Landon, Carol S; Dean, Jay B
Female rats are more susceptible to central nervous system oxygen toxicity than male rats
Abstract Tonic–clonic seizures typify central nervous system oxygen toxicity (CNS?OT) in humans and animals exposed to high levels of oxygen, as are encountered during scuba diving. We previously demonstrated that high doses of pseudoephedrine (PSE) decrease the latency to seizure (LS) for CNS?OT in young male rats. This study investigated whether female rats respond similarly to PSE and hyperbaric oxygen (HBO). We implanted 60 virgin stock (VS) and 54 former breeder (FB) female rats with radio?telemetry devices that measured brain electrical activity. One week later, rats were gavaged with saline or PSE in saline (40, 80, 120, 160, or 320 mg/kg) before diving to five atmospheres absolute in 100% oxygen. The time between reaching maximum pressure and exhibiting seizure was LS. Vaginal smears identified estrus cycle phase. PSE did not decrease LS for VS or FB, primarily because they exhibited low LS for all conditions tested. VS had shorter LS than males at 0, 40, and 80 mg/kg (?42, ?49, and ?57%, respectively). FB also had shorter LS than males at 0, 40, and 80 mg/kg (?60, ?86, and ?73%, respectively). FB were older than VS (286 ± 10 days vs. 128 ± 5 days) and weighed more than VS (299 ± 2.7 g vs. 272 ± 2.1 g). Males tested were younger (88 ± 2 days), heavier (340 ± 4.5 g), and gained more weight postoperatively (7.2 ± 1.6 g) than either VS (?0.4 ± 1.5 g) or FB (?1.6 ± 1.5 g); however, LS correlated poorly with age, body mass, change in body mass, and estrus cycle phase. We hypothesize that differences in sex hormones underlie females' higher susceptibility to CNS?OT than males.
Held, Heather E.; Pilla, Raffaele; Ciarlone, Geoffrey E.; Landon, Carol S.; Dean, Jay B.
Intestinal oxalate uptake in castrated male and female rats: evidence for altered brush border membrane composition.
The intestinal uptake rate of oxalate (mumoles/h/g tissue wt.) in castrated male (CM) rats, CM rats administered estradiol, and female (F) rats was 1.8, 1.4 and 1.3 times higher than that of male rats, whereas castrated female (CF) rats and CF rats administered testosterone absorbed oxalate at a rate similar to F rats, thereby, suggesting that gonadectomy affected intestinal uptake of oxalate only in male rats The intestinal oxalate uptake rate in all the groups increased linearly with increasing oxalate concentration (0.1- 6.0 mM). Chemical composition of brush border membrane showed significant changes in the sialic acid, phospholipid and cholesterol content following castration, which may lead to ultrastructural changes in the membrane thereby, increasing the absorption of oxalate. PMID:6477640
Sharma, V; Farooqui, S; Thind, S K; Nath, R
Effects of Quercetin on CYP450 and Cytokines in Aroclor 1254 Injured Endometrial Cells of the Pregnant Rats
Polychlorinated biphenyls (PCBs) are widespread persistent residual environmental pollutants, which affect seriously the growth and reproductive alterations in humans and animals. Aroclor 1254 is a commercial mixture of PCBs. Quercetin is a flavonoid, which acts on estrogen receptors and causes the development of estrogen-related diseases. In this paper, the primary cultured endometrial cells in the pregnant rats were isolated and Aroclor 1254 was used to induce the injured endometrial cells model. The cells were treated with gradient quercetin, the viability of the endometrial cells, the expressions of CYP450, the contents of TNF-?, IL-6, estradiol (E2), and progesterone (P4) were measured. It showed that the viability of the cultured endometrial cells, the expression of CYP1A1 and CYP2B1, and the contents of TNF-?, E2, and IL-6 in the injured endometrial cells increased with the treatment of quercetin. It shows that quercetin has protective effect on the injured endometrial cells in the pregnant rats, this provide a basis on herbal medicine protection for animal reproductive diseases caused by environmental endocrine disruptors.
Xu, Lina; Sun, Liyun; Lu, Liqin; Qin, Jianhua
Effects of Quercetin on CYP450 and Cytokines in Aroclor 1254 Injured Endometrial Cells of the Pregnant Rats.
Polychlorinated biphenyls (PCBs) are widespread persistent residual environmental pollutants, which affect seriously the growth and reproductive alterations in humans and animals. Aroclor 1254 is a commercial mixture of PCBs. Quercetin is a flavonoid, which acts on estrogen receptors and causes the development of estrogen-related diseases. In this paper, the primary cultured endometrial cells in the pregnant rats were isolated and Aroclor 1254 was used to induce the injured endometrial cells model. The cells were treated with gradient quercetin, the viability of the endometrial cells, the expressions of CYP450, the contents of TNF- ? , IL-6, estradiol (E2), and progesterone (P4) were measured. It showed that the viability of the cultured endometrial cells, the expression of CYP1A1 and CYP2B1, and the contents of TNF- ? , E2, and IL-6 in the injured endometrial cells increased with the treatment of quercetin. It shows that quercetin has protective effect on the injured endometrial cells in the pregnant rats, this provide a basis on herbal medicine protection for animal reproductive diseases caused by environmental endocrine disruptors. PMID:24711995
Xu, Lina; Sun, Liyun; Lu, Liqin; Zhong, Xiuhui; Ma, Yuzhong; Qin, Jianhua
Studies on Apoptotic Changes in Combined Toxicity of Citrinin and Endosulfan in Pregnant Wistar Rats and Their Fetuses
Background: Citrinin (mycotoxin) and endosulfan (pesticide) both environmental contaminants easily enter the food chain and are caoomon causes of various toxicities. Materials and Methods: In the present investigation, citrinin (CIT) (10 mg/kg feed) and endosulfan (1 mg/kg body weight) were administered orally alone and in combination to pregnant Wistar rats from gestational day 6 to 20 to study their effect to cause apoptosis in the pregnant Wistar rats and their fetuses. Apoptosis was assessed in dams by agarose gel electrophoresis, flow cytometry and electron microscopy, while in the fetuses it was assessed by flow cytometry only. Result: Citrinin and endosulfan in the combination group caused apoptosis in an additive manner as there was increased number of apoptotic cells as compared to the individual toxin and control groups. The fetuses also showed increased number of apoptotic cells in the combination groups, which also indicated that both the toxins crossed the placental barrier. Conclusion: So it was concluded that apoptosis played a significant role in the pathogenesis of endosulfan and citrinin toxicity.
Singh, N. D.; Sharma, A. K.; Dwivedi, P.; Telang, A. G.; Kumar, M.; Patil, R. D.
Antenatal Hypoxia Induces Programming of Reduced Arterial Blood Pressure Response in Female Rat Offspring: Role of Ovarian Function
In utero exposure to adverse environmental factors increases the risk of cardiovascular disease in adulthood. The present study tested the hypothesis that antenatal hypoxia causes a gender-dependent programming of altered arterial blood pressure response (BP) in adult offspring. Time-dated pregnant rats were divided into normoxic and hypoxic (10.5% O2 from days 15 to 21 of gestation) groups. The experiments were conducted in adult offspring. Antenatal hypoxia caused intrauterine growth restriction, and resulted in a gender-dependent increase Angiotensin II (Ang II)-induced BP response in male offspring, but significant decrease in BP response in female offspring. The baroreflex sensitivity was not significantly altered. Consistent with the reduced blood pressure response, antenatal hypoxia significantly decreased Ang II-induced arterial vasoconstriction in female offspring. Ovariectomy had no significant effect in control animals, but significantly increased Ang II-induced maximal BP response in prenatally hypoxic animals and eliminated the difference of BP response between the two groups. Estrogen replacement in ovariectomized animals significantly decreased the BP response to angiotensin II I only in control, but not in hypoxic animals. The result suggests complex programming mechanisms of antenatal hypoxia in regulation of ovary function. Hypoxia-mediated ovary dysfunction results in the phenotype of reduced vascular contractility and BP response in female adult offspring.
Xiao, DaLiao; Huang, Xiaohui; Xue, Qin; Zhang, Lubo
Microdistribution of 237Np in the skeleton of female rats.
237Np nitrate was injected intravenously into 4-week-old (young) and 10-12-week-old (adult) female albino Sprague-Dawley rats. The amounts given were 52 (young), 5.2 (adult) and 26 kBq kg-1 body weight (adult). The microscopic distribution in the femur and the lumbar vertebrae was studied. Initially, neptunium was distributed uniformly on periosteal and endosteal bone surfaces, and additionally, activity was found in the vascular canals of hard tissue. Dose-rates and cumulative doses were found to increase from marrow to hard tissue, and periosteal and endosteal surfaces, the highest levels being found in the spongy bone of the distal femoral metaphysis. Initially, the highest dose rates were found in hard tissue of the distal femoral metaphysis (27 mGy per day per injected activity of 37 kBq kg-1), whereas periosteal bone surfaces showed levels of 65 mGy per day in all bone regions. One year later the normalized dose rates on the surfaces decreased to 10 or 15 mGy per day. After 1 year the cumulative doses in the 0-10 microns marrow layer on the endosteal bone surfaces were 8 (52 kBq kg-1, young), 2.1 (5.2 kBq kg-1, adult) and 8.7 Gy (26 kBq kg-1, adult). The microdosimetric findings were compared with the macroscopical doses of the whole skeleton. PMID:8095290
Sontag, W
Standardised Models for Inducing Experimental Peritoneal Adhesions in Female Rats
Animal models for adhesion induction are heterogeneous and often poorly described. We compare and discuss different models to induce peritoneal adhesions in a randomized, experimental in vivo animal study with 72 female Wistar rats. Six different standardized techniques for peritoneal trauma were used: brushing of peritoneal sidewall and uterine horns (group 1), brushing of parietal peritoneum only (group 2), sharp excision of parietal peritoneum closed with interrupted sutures (group 3), ischemic buttons by grasping the parietal peritoneum and ligating the base with Vicryl suture (group 4), bipolar electrocoagulation of the peritoneum (group 5), and traumatisation by electrocoagulation followed by closure of the resulting peritoneal defect using Vicryl sutures (group 6). Upon second look, there were significant differences in the adhesion incidence between the groups (P < 0.01). Analysis of the fraction of adhesions showed that groups 2 (0%) and 5 (4%) were significantly less than the other groups (P < 0.01). Furthermore, group 6 (69%) was significantly higher than group 1 (48%) (P < 0.05) and group 4 (47%) (P < 0.05). There was no difference between group 3 (60%) and group 6 (P = 0.2). From a clinical viewpoint, comparison of different electrocoagulation modes and pharmaceutical adhesion barriers is possible with standardised models.
Kraemer, Bernhard; Wallwiener, Christian; Rajab, Taufiek K.; Brochhausen, Christoph; Wallwiener, Markus; Rothmund, Ralf
Opium can differently alter blood glucose, sodium and potassium in male and female rats.
To determine the effects of opium on serum glucose, potassium and sodium in male and female Wistar rat, opium solution (60 mg/kg) injected intraperitoneally and the same volume of distilled water was used as control (7 rats in each group). Blood samples were collected at 0, 30, 60, 120, 240 and 360 minutes after injection from orbit cavity and the values of serum glucose, sodium (Na(+)) and potassium (K(+)) were measured. The data were then analyzed by the repeated measure ANOVA based on sex and case-control group. P < 0.05 considered as significant difference. Serum glucose increased significantly at 30, 60, 120 and 240 minutes after opium solution injection, in female rats compared to a control group. However, the male rats had this rise at 30, 60 and 120 minutes after opium solution injection compared to control group. While serum glucose in male rats was significantly higher than females at 30, 60 and 120 minutes, this value was higher in the female rats at 360 minutes. Therefore, serum glucose alterations following opium injection was significantly different in groups and in the sexes at different times. Sodium (Na(+)) rose at 60, 240 and 360 minutes significantly in all rats compared to control group. However, sodium alteration following opium injection was significantly different only between treated and control groups but sex-independent at all times. Potassium (K(+)) increased significantly at 60, 120, 240 and 360 minutes in male rats, compared to a control group. In female rats K(+) significantly raised at 30, 120, 240 and 360 minutes. Therefore, the alteration of K(+) in male and female rats was found time dependent and sex independent. According to our results, opium increased serum glucose in male and female rats differently, and it interferes with metabolic pathways differently on a gender dependent basis. Opium raised serum Na(+) and K(+), thus it interfere with water regulation and blood pressure via different mechanism. PMID:18390449
Karam, Gholamreza Asadi; Rashidinejad, Hamid Reza; Aghaee, Mohammad Mehdi; Ahmadi, Jafar; Rahmani, Mohammad Reza; Mahmoodi, Mehdi; Azin, Hosein; Mirzaee, Mohammad Reza; Khaksari, Mohammad
Antifertility effects of (+)-S-2-amino-6-iodoacetamidohexanoic acid (2-AIHA) in female rats
(+)-S-2-amino-6-iodoacetamidohexanoic acid (AIHA), an irreversible inhibitor of the ornithindecarboxylase and extrahepatic arginase enzymatic activities with antineoplasic properties, was evaluated for antifertility activity in pregnant rats by oral administration at different periods of gestation. Our results showed that doses of 10 and 20 mg\\/kg of AIHA orally administered produced a contraceptive effect when it was administered from days 2 to 5,
German Chamorro; Maria Salazar; Silvia Salazar; Guillermo Ceballos; Jose Trujillo; Olga Munoz; Ricardo Yanez
Transplacental effects of high fat diets on functional activity of the spleen and lymph nodes, cell kinetics and apoptosis in mammary gland tumors in female rat offspring.
We studied whether feeding pregnant female rats different high fat diets affects structural zones in the spleen and lymph nodes, involved in production of T and B cells, as well as cell kinetics and apoptosis in some offspring with mammary glands tumors. Rat mothers were fed either a 7% or 15% corn-oil or a 7% or 15% olive-oil diet. At four weeks of age, female offspring (n=10-15 per group) were transferred to 7% corn oil diet. Five-week old offspring were exposed twice to the carcinogen, dimethylbenz(a)antracene (10 mg/rat/week). Three months later, tumors were counted and sized, and samples from the spleen, axillary lymph nodes and tumors collected for immunohistochemical analyses. Feeding the mothers with both the 7% and 15% olive-oil diets significantly increased the number of tumor-free rats in offspring. Tumors were characterized with active mitosis, intensive lymphoid infiltration inside a knot and high rates of apoptosis, particularly in tumors obtained from rats whose mothers were fed the 15% olive-oil diet. In the spleen, the 15% olive-oil diet significantly increased the areas of the follicles and germinal centers but only in tumor-free rats. In tumor-bearing rats, areas of germinal centers increased compared to the 7% olive-oil diet. The 15% olive-oil diet increased all areas of the lymph nodes in tumor-free rats, while in tumor-bearing rats, this diet increased the areas of the cortex and mantle layer. We conclude that exposure to various diets in utero and during lactation affects the immune system. In addition, the promotion of apoptosis may play a key role in the mechanisms involved in the transplacental effects on mammary tumor development as seen using a 15% olive-oil diet, similar to the high fat diets of Mediterranean countries. PMID:12430006
Kossoy, George; Stark, Aliza; Tendler, Yevgenie; Ben-Hur, Herzl; Beniashvili, Dzhemali; Madar, Zecharia; Zusman, Itshak
Excess androgen during puberty disrupts circadian organization in female rats.
Circadian clocks have been described in each tissue of the hypothalamo-pituitary-ovarian axis. Although a role for the clock in the timing of ovulation is indicated, the impact of diseases that disrupt fertility on clock function or the clocks' role in the etiology of these pathologies has yet to be fully appreciated. Polycystic ovary syndrome (PCOS) is a particularly devastating endocrinopathy, affecting approximately 10% of women at childbearing age. Common features of PCOS are a polycystic ovary, amenorrhea, and excess serum androgen. Approximately 40% of these women have metabolic syndrome, including hyperinsulinemia, dyslipidemia, and hyperleptinemia. It has been suggested that excess androgen is a critical factor in the etiology of PCOS. We have examined the effects of androgen excess during puberty on the phase of circadian clocks in tissues of the metabolic and hypothalamo-pituitary-ovarian axes. Female period1-luciferase (per1-luc) rats were exposed to androgen (5?-dihydrotestosterone [DHT]) or placebo for 4-6 weeks (short term) or 9-15 weeks (long term). As expected, DHT-treated animals gained more weight than controls and had disrupted estrous cycles. At the end of treatment, tissues, including the liver, lung, kidney, white adipose, cornea, pituitary, oviduct, and ovarian follicles, were cultured, and per1-luc expression in each was recorded. Analysis of per1-luc expression revealed that DHT exposure increased phase distribution of multiple oscillators, including ovarian follicles, liver, and adipose, and altered phase synchrony between animals. These data suggest that excess androgen during puberty, a common feature of PCOS, negatively affects internal circadian organization in both the reproductive and metabolic axes. PMID:23417420
Sellix, Michael T; Murphy, Zachary C; Menaker, Michael
Excess Androgen During Puberty Disrupts Circadian Organization in Female Rats
Circadian clocks have been described in each tissue of the hypothalamo-pituitary-ovarian axis. Although a role for the clock in the timing of ovulation is indicated, the impact of diseases that disrupt fertility on clock function or the clocks' role in the etiology of these pathologies has yet to be fully appreciated. Polycystic ovary syndrome (PCOS) is a particularly devastating endocrinopathy, affecting approximately 10% of women at childbearing age. Common features of PCOS are a polycystic ovary, amenorrhea, and excess serum androgen. Approximately 40% of these women have metabolic syndrome, including hyperinsulinemia, dyslipidemia, and hyperleptinemia. It has been suggested that excess androgen is a critical factor in the etiology of PCOS. We have examined the effects of androgen excess during puberty on the phase of circadian clocks in tissues of the metabolic and hypothalamo-pituitary-ovarian axes. Female period1-luciferase (per1-luc) rats were exposed to androgen (5?-dihydrotestosterone [DHT]) or placebo for 4-6 weeks (short term) or 9-15 weeks (long term). As expected, DHT-treated animals gained more weight than controls and had disrupted estrous cycles. At the end of treatment, tissues, including the liver, lung, kidney, white adipose, cornea, pituitary, oviduct, and ovarian follicles, were cultured, and per1-luc expression in each was recorded. Analysis of per1-luc expression revealed that DHT exposure increased phase distribution of multiple oscillators, including ovarian follicles, liver, and adipose, and altered phase synchrony between animals. These data suggest that excess androgen during puberty, a common feature of PCOS, negatively affects internal circadian organization in both the reproductive and metabolic axes.
Murphy, Zachary C.; Menaker, Michael
Functional and Neuroanatomical Effects of Vaginal Distention and Pudendal Nerve Crush in the Female Rat
PurposeWe tested the hypothesis that neuroanatomical degeneration near the external urethral sphincter (EUS) would parallel urinary dysfunction after vaginal distention or bilateral pudendal nerve crush in female rats.
Regional differences in the pituitary distribution of luteinizing hormone in the gonadectomized and proestrous female rat
Previous data have shown regional differences in the presence of anterior pituitary luteinizing hormone (LH) that generally correlate with comparable disparities in the distribution of gonadotropes throughout the gland. In female rats, the differences are apparent over the estro...
Nicotine-Induced Antinociception in Male and Female Sprague-Dawley Rats.
National Technical Information Service (NTIS)
Nicotine is a key pharmacologically-active ingredient in tobacco that has cognitive and behavioral effects, including antinociception. The present research examined effects of nicotine as an antinociceptive agent in male and female Sprague-Dawley rats. Ni...
N. Apatov
Toxic effects of zearalenone on oxidative stress, inflammatory cytokines, biochemical and pathological changes induced by this toxin in the kidney of pregnant rats.
An experiment was conducted to determine the toxic effects of zearalenone (ZEN) on oxidative stress, inflammatory cytokines, biochemical and pathological changes in the kidney of pregnant rats, and to explore the possible mechanism in ZEN induced kidney damage. The rats were fed a normal diet treated with 0.3, 48.5, 97.6 or 146 mg/kg ZEN in feed on gestation days (GDs) 0 through 7, and then all the rats were fed with a normal diet on GDs 8 through 20. The results showed that ZEN induced kidney dysfunction, oxidative damage, pathological changes and increased mRNA and protein expression of TLR4 and inflammatory cytokines in kidney in dose-dependent manner. The results indicated that ZEN caused kidney damage of pregnant rats and TLR4-mediated inflammatory reactions signal pathway was one of the mechanisms of ZEN mediated toxicity in kidney. PMID:24562056
Jia, Zhiqiang; Liu, Min; Qu, Zhe; Zhang, Yuanyuan; Yin, Shutong; Shan, Anshan
Corticotrophin releasing factor (CRF) induced reinstatement of cocaine seeking in male and female rats
Significant sex differences have been demonstrated in clinical and preclinical studies of cocaine addiction, with some of the most consistent differences noted in regards to the role of stress and craving. The current study examined stress-induced reinstatement of cocaine seeking in male and female rats in an animal model of relapse using corticotropin-releasing factor (CRF) administration. Both male and female rats demonstrated increased cocaine seeking in response to CRF. CRF-induced reinstatement was highly variable across both male and female rats, and further analysis revealed a subpopulation that was particularly sensitive to CRF (high responders). Female high responders displayed significantly increased responding to CRF compared to males. Individual differences in stress responsivity could thus contribute to the likelihood of relapse, with females showing greater heterogeneity to stress-induced relapse.
Buffalari, Deanne M.; Baldwin, Chelsey K.; Feltenstein, Matthew W.; See, Ronald E.
In vivo evidence for a greater brain tryptophan hydroxylase capacity in female than in male rats
Previous studies have revealed that brain levels of tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) are moderately higher in female than in male rats. Since tryptophan hydroxylase is only about half saturated with substrate, the greater availability of precursor in female rats might contribute to their higher 5-hydroxyindole levels. The present investigation was aimed at clarifying whether there is a
Maria Carlsson; Arvid Carlsson
Sex Steroid Regulation of the Inflammatory Response: Sympathoadrenal Dependence in the Female Rat
To investigate the role of sex steroids in sex differences in the response of rats to the potent inflammatory mediator bradykinin (BK), we evaluated the effect of sex steroid manipulation on the magnitude of BK-induced synovial plasma extravasation (PE). The magnitude of BK-induced PE is markedly less in females. Ovariectomy of female rats increased BK-induced PE, and administration of 17b-estradiol
Paul G. Green; Solbritt RantapaaDahlqvist; William M. Isenberg; Holly J. Strausbaugh; Frederick J.-P. Miao; Jon D. Levine
Functional and morphological modifications of the urinary bladder in aging female rats
Functional and morphological modifications of the urinary bladder in aging female rats. Am J Physiol Regulatory Integrative Comp Physiol 278: R964-R972, 2000.—In female Wistar\\/Rij rats, 10 and 30 mo old, the micturition profiles in conscious animals, the contractile responses of the isolated urinary bladder, and the histology of the vesical tissue have been investigated. During cystomanometry, 60% of conscious senescent
Role of estrogen in the acquisition of intravenously self-administered cocaine in female rats
Previous work from this laboratory has revealed that female rats acquired cocaine self-administration at a faster rate than male rats and that a greater percentage of females acquired self-administration [Psychopharmacology 144 (1999) 77.]. It has been suggested that sex differences in stimulant self-administration may be related to ovarian hormones, particularly estrogen. To investigate this possibility, we compared four groups (n=10)
Wendy J Lynch; Megan E Roth; Jennifer L Mickelberg; Marilyn E Carroll
Differential regulation of seizure activity in the hippocampus of male and female rats
OBJECTIVE: The aim of the current study was to directly examine and compare the susceptibility to N-methyl-D-aspartate-induced seizures in male versus female rats. We Also sought to compare the anticonvulsant effects of magnesium sulfate in these two groups.STUDY DESIGN: Eighteen female and 10 male rats were stereotaxically implanted with a chronic bipolar recording electrode in the hippocampus and an injection
Cynthia A. Standley; Brian A. Mason; David B. Cotton
Prenatal alcohol exposure reduces the proportion of newly produced neurons and glia in the dentate gyrus of the hippocampus in female rats
Prenatal alcohol exposure (PAE) alters adult neurogenesis and the neurogenic response to stress in male rats. As the effects of stress on neurogenesis are sexually dimorphic, the present study investigated the effects of PAE on adult hippocampal neurogenesis under both non-stressed and stressed conditions in female rats. Pregnant females were assigned to one of three prenatal treatments: 1) Alcohol (PAE) - liquid alcohol (ethanol) diet ad libitum (36% ethanol-derived calories); 2) Pair-fed - isocaloric liquid diet, with maltose-dextrin substituted for ethanol, in the amount consumed by a PAE partner (g/kg body wt/day of gestation); and 3) Control - lab chow ad libitum. Female offspring were assigned to either non-stressed (undisturbed) or stressed (repeated restraint stress for 9 days) conditions. On day 10, all rats were injected with bromodeoxyuridine (BrdU) and perfused either 24 hours (cell proliferation) or 3 weeks (cell survival) later. We found that PAE did not significantly alter cell proliferation or survival, whereas females from the Pair-fed condition exhibited elevated levels of cell survival compared to Control females. Importantly, however, the proportion of both new neurons and new glial cells in the hippocampal dentate gyrus was reduced in PAE compared to Control females. Exposure to stress did not alter neurogenesis in any of the prenatal treatment groups. In summary, compared to females from the Control condition, prenatal dietary restriction enhanced the survival of new neurons, whereas PAE altered the differentiation of newly produced cells in the adult dentate gyrus. Alterations in hippocampal neurogenesis following PAE may contribute to learning and memory deficits seen in individuals with fetal alcohol spectrum disorders.
Uban, Kristina A.; Sliwowska, Joanna H.; Lieblich, Stephanie; Ellis, Linda A.; Yu, Wayne L.; Weinberg, Joanne; Galea, Liisa A. M.
14-C-Naphthyl, 14-C-Methyl and 14-C-Carbonyl Carbaryl Distribution in the Pregnant Mouse and Rat.
National Technical Information Service (NTIS)
The distribution of carbaryl labeled with 14C in the ring, methyl or carbonyl groups was determined in pregnant mice and rats. Three identical concurrent experiments were performed using each of the three radiolabeled compounds in each of the species so t...
K. D. Courtney J. E. Andrews M. A. Grady
Behavioral effects of nicotine withdrawal in adult male and female rats.
Nicotine withdrawal may differ between men and women but clinical reports are inconsistent. Two experiments were conducted to examine behavioral effects of nicotine withdrawal in male and female adult rats in dimly-lit and brightly-lit environments. Ninety-six Sprague-Dawley male and female rats received 7 days continuous subcutaneous infusion via ALZET osmotic minipumps filled with saline or 3.16 mg/kg/day nicotine hydrogen tartrate expressed as base. Behavioral observations were made before, during, and after drug administration. During observations, occurrences of empty-mouth-chewing, whole-body-shakes, abnormal grooming, abnormal posture/movement, diarrhea, ptosis, eyeblinks, and any other abnormal behaviors were counted. Cessation of nicotine administration upon pump removal caused a significant increase in withdrawal behaviors in males and females in both environments. In the dimly-lit environment, females showed more withdrawal behavior than males; there was no sex difference in the brightly-lit environment. Males that had received nicotine displayed more withdrawal behavior in the brightly-lit environment than in the dimly-lit environment, while females that had received nicotine displayed similar amounts of withdrawal behavior in both environments. Behavioral symptoms of withdrawal may be more affected by the environment in male rats than in female rats. These experiments are the first to compare nicotine withdrawal in adult male and female rats. PMID:19000707
Hamilton, Kristen R; Berger, Sarah Shafer; Perry, Michael E; Grunberg, Neil E
Effect of Long-term Fluoride Exposure on Lipid Peroxidation and Histology of Testes in First and Second-generation Rats
This experiment was designed to investigate the histological and lipid peroxidation effects of chronic fluorosis on testes\\u000a tissues of first- and second-generation rats. Sixteen virgin female Wistar rats were mated with eight males (2:1) for approximately\\u000a 12 h to obtain first-generation rats. Pregnant rats were divided into two groups: controls and fluoride-given group, each\\u000a of which containing five rats. Pregnant rats
Meral Öncü; Ahmet Kocak; Erdal Karaoz; Hakan Darici; Emin Savik; Fatih Gultekin
Endothelial-derived hyperpolarization factor (EDHF) contributes to PlGF-induced dilation of mesenteric resistance arteries from pregnant rats.
The aim of this study was to investigate the cellular mechanism involved in the potent vasodilatory action of PlGF on mesenteric resistance arteries from pregnant rats. PlGF (3 nM) induced a vasodilation of 64 ± 3.8% that was completely abolished by endothelial denudation. Significant dilation (28 ± 4.0%) remained, however, in the presence of nitric oxide synthase and cyclooxygenase inhibition, and was associated with significant reductions in vascular smooth muscle cell calcium. Absence of dilation in potassium-depolarizing solution (30 mM) confirmed its dependence on endothelial-derived hyperpolarization factor. Subsequent studies established that vasodilation was abolished by pharmacologic inhibition of SK(Ca) (apamin) and BK(Ca) (iberiotoxin) but not IK(Ca) (tram-34) potassium channels. In summary, PlGF acts through the release of a combination of endothelium-derived relaxation factors. Based on the results of potassium channel blockade, we suggest that it induces endothelial hyperpolarization via SK(Ca) channel activation; this, in turn, leads to the release of a diffusible mediator that activates vascular smooth muscle BK(Ca) channels, hyperpolarization and vasodilation. This is the first study to identify the mechanism for PlGF/VEGFR-1 resistance artery dilation in the pregnant state, whose attenuation likely contributes to the systemic hypertension characteristic of pre- eclampsia. PMID:21985802
Mandalŕ, Maurizio; Gokina, Natalia; Barron, Carolyn; Osol, George
Changes in geometrical and biomechanical properties of immature male and female rat tibia
NASA Technical Reports Server (NTRS)
The differences in the geometry and mechanical properties of immature male and female rat tibiae were detailed in order to provide comparative data for spaceflight, exercise, or disease experiments that use immature rats as an animal model. The experiment focuses on the particularly rapid period of growth that occurs in the Sprague-Dawley rat between 40 and 60 d of age. Tibial length and middiaphysical cross-sectional data were analyzed for eight different groups of rats according to age and sex, and tibial mechanical properties were obtained via three-point bending tests to failure. Results indicate that, during the 15 d period of rapid growth, changes in rat tibial geometry are more important than changes in bone material properties for influencing the mechanical properties of the tibia. Male tibiae changed primarily in structural properties, while in the female rats major changes in mechanical properties of the tibia were only attributable to changes in the structural properties of the bone.
Zernicke, Ronald F.; Hou, Jack C.-H.; Vailas, Arthur C.; Nishimoto, Mitchell; Patel, Sanjay
Effect of conazole fungicides on reproductive development in the female rat
Three triazole fungicides were evaluated for effects on female rat reproductive development. Rats were exposed via feed to propiconazole (P) (100, 500, or 2500ppm), myclobutanil (M) (100, 500, or 2000ppm), or triadimefon (T) (100, 500, or 1800ppm) from gestation day 6 to postnatal day (PND) 98. Body weight (BW) and anogenital distance (AGD) at PND 0, age and BW at
John C. Rockett; Michael G. Narotsky; Kary E. Thompson; Inthirany Thillainadarajah; Chad R. Blystone; Amber K. Goetz; Hongzu Ren; Deborah S. Best; Rachel N. Murrell; Harriette P. Nichols; Judith E. Schmid; Douglas C. Wolf; David J. Dix
Growth Hormone Secretion Is Differently Affected in Genetically Obese Male and Female Rats
Growth hormone (GH) secretion is markedly blunted in obesity. Reportedly, genetically obese Zucker rats show a reduced GH secretion due to an impaired function of hypothalamic neurons producing the GH-releasing hormone (GHRH). The aim of this work was: (1) to compare the in vitro GH responsiveness to GHRH in genetically obese female versus male Zucker rats and, (2) to evaluate
Daniela Cocchi; Marco Parenti; Lorena Cattaneo; V. De Gennaro Colonna; Andrea Zocchetti; Eugenio E. Müller
Oral contraceptive administration aggravates nitric oxide synthesis inhibition-induced high blood pressure in female rats
The use of estrogen–progestogen oral contraceptive (OC) is associated with high blood pressure, although mechanisms responsible are still unclear. This study sought to investigate the effects of administration of OC on high blood pressure resulting from nitric oxide (NO) synthesis inhibition in female Sprague–Dawley rats. Rats were given ethinyl estradiol in combination with norgestrel and were treated with NO synthase
L. A. Olatunji; A. O. Soladoye
The Role of Clomipramine in Potentiating the Teratogenic Effects of Caffeine in Pregnant Rats: A Histopathological Study
Since little is known about the teratogenic effects of clomipramine used concurrently with caffeine during the organogenesis period, the aim of this study was to test the teratogenic effects of a coadministration of caffeine and clomipramine on rat fetuses. We divided 42 pregnant rats into seven groups, randomly. The first group (control) received 0.5?mL of normal saline. Clomipramine was injected at 40?mg/kg and 80?mg/kg to the second and third groups, respectively. The fourth and fifth groups received caffeine in doses of 60?mg/kg and 120?mg/kg, respectively. The sixth group received a combination of 40?mg/kg clomipramine and 60?mg/kg caffeine, and the seventh group was given clomipramine and caffeine at 80?mg/kg and 120?mg/kg, respectively. The fetuses were removed on the 17th day of pregnancy and studied in terms of microscopic and macroscopic morphological features. Fetuses of rats receiving high doses of caffeine or combinations of caffeine and clomipramine showed a significant rate of cleft palate development, open eyelids, mortality, torsion anomalies, shrinkage of skin, and subcutaneous haemorrhage (P ? 0.001). This study concludes that caffeine in high doses or the simultaneous administration of caffeine and clomipramine leads to teratogenicity.
Nikoui, Vahid; Ostadhadi, Sattar; Takzare, Nasrin; Nabavi, Seyyed Mohammad-Ali; Bakhtiarian, Azam
Effect of Symplocos racemosa Roxb. on gonadotropin release in immature female rats and ovarian histology
In the present study we are reporting in vivo effect of aqueous extracts of Symplocos racemosa Roxb. (Fam. Symplocaceae) on serum FSH and LH levels in immature female Sprague–Dawley rats under basal conditions. Symplocos racemosa is used in Indian System of Medicine (ISM) for various female disorders. Aqueous extract on oral administration significantly stimulated serum FSH level (P < 0.016)
Kamlesh Kumar Bhutani; Atul N Jadhav; Vandana Kalia
[Role of oxytocin in activation of spontaneous electrical activity of uterine body and uterine tubes in non-pregnant rats].
The work studies effects of various doses of oxytocin (0.01, 0.1, 1 and 10 microg/kg) on duration of discharges of spontaneous electrical activity and frequency of spikes in various parts of uterine tubes and of uterine body of non-pregnant rats. Under these conditions, changes in these parameters for ovarian parts of the uterine tubes had similar character unlike those in cervical parts of the tubes and in the middle part of the uterine body, so the latter parts can be grouped together owing to peculiarities of their changes. The longest duration of genesis of electric discharges has been shown for the ovarian part of uterine tubes at a concentration of 10 microg/kg of oxytocin. Morphological experiments revealed that among all studies areas the ovarian parts of uterine tubes were characterized by the highest amount of atypical cells that have the maximally pronounced functional activity. PMID:21780644
Kazarian, K V; Unanian, N G; Meliksetian, I B; Akopian, R R; Saakian, A A
The accumulation and histological effects of organometallic fungicides Propineb and Maneb in the kidneys of fetus and female rats during pregnancy.
Dithiocarbamate propineb and maneb are organometal fungicides, which are widely used for the control of diseases in plants. Female Wistar rats were exposed orally to 200 and 400 ppm propineb and 250 ppm maneb, from the sixth day of gestation up to birth. We found that the body weights of both one-day old litters and their fungicide-treated mothers were lower than those of controls. Histological examination of the kidneys of fetus and fungicide-treated pregnant females showed a variety of histopathological effects. Moreover, the analysis of zinc (Zn) and manganese (Mn) concentrations (using inductively coupled plasma-atomic emission spectrometry) in the kidneys of pregnant females exposed to organometallic fungicides during pregnancy demonstrated that the metal concentrations in the kidney were higher than those of controls. However, the renal metal concentrations were significantly increased in the litters subjected to the fungicides during gestation, indicating that high levels of the trace metals in the organ of fetus may well be due to the fungicides easily passing the placental barrier. PMID:9817080
Guven, K; Deveci, E; Akba, O; Onen, A; de Pomerai, D
Maternal care associates with play dominance rank among adult female rats.
Variations in maternal care influence important life history traits that determine reproductive fitness. The adult female offspring of mothers that show reduced levels of pup licking/grooming (LG; i.e., low-LG mothers) show increased defensive responses to stress, accelerated pubertal development, and greater sexual receptivity than the female offspring of high-LG mothers. Amongst several species an accelerated pattern of reproductive development is associated with increased dominance-related behaviors and higher social rank. We hypothesize that rats from low-LG dams may thus also secure higher social rank as a means to compete for limited resources with conspecifics. In this study, social interactions were observed in triads of adult female rats aged p90 that received low, mid, and high levels of pup LG over the first week of life. Low- and mid-LG females had the highest pinning scores and high-LG rats the lowest, showing that low- and mid-LG adult females engage in greater play dominance-related behavior. Likewise, low- and mid-LG rats spent significantly more time drinking following 24?hr of water deprivation in a water competition test thus allowing them to secure a limited resource more easily than high-LG rats. Interestingly, pinning by play dominant females was increased when subordinates were sexually receptive (proestrus/estrus), suggestive of a process of reproductive suppression. Some evidence suggests that low-LG and mid-LG rats also show greater fecundity than high-LG rats. Variations in maternal care may thus have a long-term influence on the development of play dominance and possibly social rank in the female rat, which might contribute to reproductive success within a competitive environment. PMID:22786820
Parent, Carine I; Del Corpo, Adina; Cameron, Nicole M; Meaney, Michael J
Reinstatement of methamphetamine seeking in male and female rats treated with modafinil and allopregnanolone
Background Sex differences in methamphetamine (METH) use (females>males) have been demonstrated in clinical and preclinical studies. This experiment investigated the effect of sex on the reinstatement of METH-seeking behavior in rats and to determine whether pharmacological interventions for METH-seeking behavior vary by sex. Treatment drugs were modafinil (MOD), an analeptic, and allopregnanolone (ALLO), a neuroactive steroid and progesterone metabolite. Method Male and female rats were trained to self-administer i.v. infusions of METH (0.05mg/kg/infusion). Next, rats self-administered METH for a 10-day maintenance period. METH was then replaced with saline, and rats extinguished lever-pressing behavior over 18 days. A multi-component reinstatement procedure followed where priming injections of METH (1 mg/kg) were administered at the start of each daily session, preceded 30 min by MOD (128 mg/kg, i.p.), ALLO (15 mg/kg, s.c.), or vehicle treatment. MOD was also administered at the onset of the session to determine if it would induce the reinstatement of METH-seeking behavior. Results Female rats had greater METH-induced reinstatement responding compared to male rats following control treatment injections. MOD (compared to the DMSO control) attenuated METH-seeking behavior in male and female rats; however, ALLO only reduced METH-primed responding in females. MOD alone did not induce the reinstatement of METH-seeking behavior. Conclusions These results support previous findings that females are more susceptible to stimulant abuse compared to males and ALLO effectively reduced METH-primed reinstatement in females. Further, they illustrate the utility of MOD as a potential agent for prevention of relapse to METH use in both males and females.
Holtz, Nathan A; Lozama, Anthony; Prisinzano, Thomas E; Carroll, Marilyn E
Chronic anti-phencyclidine monoclonal antibody therapy decreases phencyclidine-induced in utero fetal mortality in pregnant rats
Illicit drug use during pregnancy is a serious social and public health problem inflicting an array of deleterious effects on both mother and offspring. We investigated the hypothesis that a murine anti-phencyclidine (PCP) monoclonal antibody (mAb6B5; KD=1.3 nM) can safely protect mother and fetus from PCP-induced adverse health effects in pregnant rats. Pregnant Sprague-Dawley rats (n=4–5) were intravenously administered bolus injections of PCP (1 mg/kg) on multiple days during pregnancy. They were also chronically treated with anti-PCP mAb6B5 at 45 mg/kg as a PCP antagonist. This dose provided one mAb-PCP binding site for every four PCP molecules. Therapeutic and safety study endpoints included pregnancy outcome (litter size, number of live vs. dead pups), maternal hemodynamic status and locomotor activity. Maternal hemodynamic changes (i.e., blood pressure and heart rate) and locomotor activity were measured in dams from gestation days 6–21 (one day antepartum) using a radiotelemetry-tracking device with a femoral arterial pressure catheter. This mAb6B5 treatment regimen significantly (p=0.008) reduced the number of PCP-induced in utero fetal deaths (odds ratio=3.2; 95%CI 1.3 to 7.9) and significantly (p<0.05) reduced acute PCP-induced maternal locomotor effects in the second trimester. Maternal hemodynamic responses to PCP were not significantly affected by mAb6B5 treatment. In conclusion, these data suggest that anti-PCP mAb treatments administered during pregnancy can safely protect a mother and her fetus(es) from PCP-related morbidity and mortality even when the mAb dose is too low to significantly prevent other PCP-induced maternal pharmacological effects.
Hubbard, JJ; Laurenzana, EM; Williams, DK; Gentry, WB; Owens, SM
Pituitary leptin gene expression is reduced by neonatal androgenization of female rats.
We have previously reported evidence of leptin gene expression (ob mRNA) in adult rat brain and pituitary gland. We have also shown that ob mRNA levels in female rat brain and pituitary are regulated in an age- and tissue-dependent fashion. In view of the known sexual dimorphism in adipose tissue leptin expression, we have extended our original work to include an assessment of ob mRNA levels in brain, pituitary and fat of developing male and female rats. In addition we determined the effects of neonatal androgenization of female rat pups with testosterone propionate. Leptin (ob) mRNA expression was evaluated using semi-quantitative RT-PCR analysis. Leptin mRNA levels were developmentally regulated in the pituitary and cortex of male rats, paralleling the changes previously observed in female rats. In the pituitary, leptin expression was significantly higher during the early postnatal period and dropped abruptly by postnatal day (PD) 22. In the cortex, leptin expression was lowest at PD 4 and rose significantly by PD 14. In addition gender differences, most notably in the pituitary, were also observed. In pituitary gland, ob mRNA was significantly higher in female rats than in males at PD 14 (+60%; p < 0.05) but there were no sex differences at PD 4 and PD 22. Testosterone treatment of neonatal female rats profoundly reduced ob mRNA at PD 14 (3.5-fold; p < 0.01) and PD 22 (3-fold; p = 0.05). In subcutaneous adipose tissue and hypothalamus we observed no sex difference in ob mRNA levels nor an effect of testosterone. We conclude that leptin gene expression in rat pituitary gland is sexually dimorphic and sensitive to neonatal manipulation of sex steroid levels. PMID:11824509
Morash, B A; Ur, E; Wilkinson, M
Growth hormone exacerbates diabetic renal damage in male but not female rats
Background Human and animal studies support the idea that there are sex differences in the development of diabetic renal disease. Our lab and others have determined that in addition to Ang II (through the AT1R), growth hormone (GH) contributes to renal damage in models of renal failure; however, the impact of sex and GH on the mechanisms initiating diabetic renal disease is not known. This study examined the effect of sex and GH on parameters of renal damage in early, uncontrolled streptozotocin (STZ)-induced diabetes. Methods Adult male and female Sprague–Dawley rats were injected with vehicle (control), STZ, or STZ?+?GH and euthanized after 8 weeks. Results Mild but significant glomerulosclerosis (GS) and tubulointerstitial fibrosis (TIF) was observed in both kidneys from male and female diabetic rats, with GH significantly increasing GS and TIF by 30% and 25% in male rats, but not in female rats. STZ increased TGF-? expression in both kidneys from male and female rats; however, while GH had no further effect on TGF-? protein in diabetic females, GH increased TGF-? protein in the male rat's kidneys by an additional 30%. This sex-specific increase in renal injury following GH treatment was marked by increased MCP-1 and CD-68+ cell density. STZ also reduced renal MMP-2 and MMP-9 protein expression in both kidneys from male and female rats, but additional decreases were only observed in GH-treated diabetic male rats. The sex differences were independent of AT1R activity. Conclusions These studies indicate that GH affects renal injury in diabetes in a sex-specific manner and is associated with an increase in pro-inflammatory mediators.
Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats.
Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse. PMID:24878606
Souza, M F; Couto-Pereira, N S; Freese, L; Costa, P A; Caletti, G; Bisognin, K M; Nin, M S; Gomez, R; Barros, H M T
Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats
Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.
Souza, M.F.; Couto-Pereira, N.S.; Freese, L.; Costa, P.A.; Caletti, G.; Bisognin, K.M.; Nin, M.S.; Gomez, R.; Barros, H.M.T.
Expression of cytochrome CYP2B1\\/2 in nonpregnant, pregnant and fetal rats exposed to tobacco smoke
Four-month-old female Wistar rats were exposed for 20 days to tobacco smoke ob- tained from non-filter cigarettes. During the exposure, concentration of tobacco smoke was monitored indirectly by measuring the CO level (1500 mg\\/m 3 air). The effi- cacy of exposure was assessed by measuring urine nicotine and cotinine levels. Ciga- rette smoke did not change total cytochrome P450 and
Piotr Czekaj; Anna Wiaderkiewicz; Ewa Florek; Ryszard Wiaderkiewicz
Female rats are more susceptible to the deleterious effects of paradoxical sleep deprivation on cognitive performance.
Paradoxical sleep deprivation (PSD) may alter subsequent learning and memory capacity. There are differences in both the intensity and direction of responses of the male and female species to the same environmental stimuli and experimental conditions. In the present study, we examined the extent of the effects of PSD for 72h on spatial learning and memory, anxiety-like behavior, corticosterone levels, and the body weight in male as well as in intact and ovariectomized (OVX) female Wistar rats. Multiple platform method was used for PSD induction. Spatial learning and memory and anxiety-like behavior were determined using Morris water maze (MWM) task and open field test, respectively. The data showed that PSD could not significantly affect subsequent spatial learning and short-term memory in male rats, while it significantly impaired the performance of the intact and OVX female rats. The PSD-intact and -OVX female rats showed more memory impairment than the PSD-male animals. Those impairments do not appear to be due to elevated stress level, since the plasma corticosterone did not significantly change following PSD induction. The open field data showed that PSD significantly reduced anxiety-like behavior in all experimental groups. In addition, PSD had a reducing effect on the mean body weight of female groups. Such results suggest that the female rats are more vulnerable to the deleterious effects of sleep loss on cognitive performance. PMID:22192378
Hajali, Vahid; Sheibani, Vahid; Esmaeili-Mahani, Saeed; Shabani, Mohammad
Toxoplasma gondii influences aversive behaviors of female rats in an estrus cycle dependent manner.
The protozoan Toxoplasma gondii (T. gondii) manipulates the behavior of its rodent intermediate host to facilitate its passage to its feline definitive host. This is accomplished by a reduction of the aversive response that rodents show towards cat odors, which likely increases the predation risk. Females on average show similar changes as males. However, behaviors that relate to aversion and attraction are usually strongly influenced by the estrus cycle. In this study, we replicated behavioral effects of T. gondii in female rats, as well as expanded it to two novel behavioral paradigms. We also characterized the role of the estrus cycle in the behavioral effects of T. gondii on female rats. Uninfected females preferred to spend more time in proximity to rabbit rather than bobcat urine, and in a dark chamber rather than a lit chamber. Infected females lost both of these preferences, and also spent more time investigating social novelty (foreign bedding in their environment). Taken together, these data suggest that infection makes females less risk averse and more exploratory. Furthermore, this effect was influenced by the estrus cycle. Uninfected rats preferred rabbit urine to bobcat urine throughout the cycle except at estrus and metestrus. In contrast, infected rats lost this preference at every stage of the cycle except estrus. Commensurate with the possibility that this was a hormone-dependent effect, infected rats had elevated levels of circulating progesterone, a known anxiolytic. PMID:24907696
Golcu, Doruk; Gebre, Rahiwa Z; Sapolsky, Robert M
In Utero and Lactational Exposures to Low Doses of Polybrominated Diphenyl Ether-47 Alter the Reproductive System and Thyroid Gland of Female Rat Offspring
Background Polybrominated diphenyl ethers (PBDEs) are capable of disrupting thyroid hormone homeostasis. PBDE-47 (2,2?,4,4?-tetrabromodiphenyl ether) is one of the most abundant congeners found in human breast adipose tissue and maternal milk samples. Objectives We evaluated the effects of developmental exposure to low doses of PBDE-47 on the female reproductive system. Methods Pregnant Wistar rats were administered vehicle (peanut oil) or PBDE-47 [140 or 700 ?g/kg body weight (bw)] on gestation day (GD) 6, or 5 mg 6-n-propyl-2-thiouracil (PTU)/L in the drinking water from GD7 through postnatal day (PND) 21. Results In female offspring sacrificed on PND38, there was a significant decrease in ovarian weight after exposure to PTU or 140 ?g/kg PBDE-47. Alterations in folliculogenesis were apparent: we observed a decrease in tertiary follicles and serum estradiol concentrations in the offspring exposed to either PTU or 700 ?g/kg PBDE-47. PTU exposure also resulted in a decrease in primordial follicles. On PND100, persistent effects on the thyroid glands included histologic and morphometric changes after exposure to either PTU or PBDE-47. No relevant changes in reproductive indices were observed after mating the exposed F1 females with nontreated males. Conclusions Administration of PBDE-47 at doses relevant to human exposure led to changes in the rat female reproductive system and thyroid gland.
Talsness, Chris E.; Kuriyama, Sergio N.; Sterner-Kock, Anja; Schnitker, Petra; Grande, Simone Wichert; Shakibaei, Mehdi; Andrade, Anderson; Grote, Konstanze; Chahoud, Ibrahim
Functional determination of oxytocin affinity in near-term pregnant rat myometrium: effect of chronic hypoxia
We designed the present study to determine: (1) if phenoxybenzamine can be used as an irreversible blocker for oxytocin receptors, and as such to determine oxytocin affinity, (2) if prolonged hypoxic exposure alters oxytocin receptor coupling efficacy of oxytocin receptors to post-receptor mediated mechanisms in the rat myometrium. Rats were exposed to room air (control), or to continuous hypoxia (10.5%
Joon W. Rhee; Lubo Zhang; Charles A. Ducsay
A boundary-representation method for designing whole-body radiation dosimetry models: pregnant females at the ends of three gestational periods—RPI-P3, -P6 and -P9
NASA Astrophysics Data System (ADS)
Fetuses are extremely radiosensitive and the protection of pregnant females against ionizing radiation is of particular interest in many health and medical physics applications. Existing models of pregnant females relied on simplified anatomical shapes or partial-body images of low resolutions. This paper reviews two general types of solid geometry modeling: constructive solid geometry (CSG) and boundary representation (BREP). It presents in detail a project to adopt the BREP modeling approach to systematically design whole-body radiation dosimetry models: a pregnant female and her fetus at the ends of three gestational periods of 3, 6 and 9 months. Based on previously published CT images of a 7-month pregnant female, the VIP-Man model and mesh organ models, this new set of pregnant female models was constructed using 3D surface modeling technologies instead of voxels. The organ masses were adjusted to agree with the reference data provided by the International Commission on Radiological Protection (ICRP) and previously published papers within 0.5%. The models were then voxelized for the purpose of performing dose calculations in identically implemented EGS4 and MCNPX Monte Carlo codes. The agreements of the fetal doses obtained from these two codes for this set of models were found to be within 2% for the majority of the external photon irradiation geometries of AP, PA, LAT, ROT and ISO at various energies. It is concluded that the so-called RPI-P3, RPI-P6 and RPI-P9 models have been reliably defined for Monte Carlo calculations. The paper also discusses the needs for future research and the possibility for the BREP method to become a major tool in the anatomical modeling for radiation dosimetry.
Xu, X. George; Taranenko, Valery; Zhang, Juying; Shi, Chengyu
Selenium and vitamin E modulates radiation-induced liver toxicity in pregnant and nonpregnant rat: effects of colemanite and hematite shielding.
The levels of liver lipid peroxidation, glutathione peroxidase, reduced glutathione, and vitamins A and E were used to follow the level of oxidative damage caused by ionizing radiation in pregnant rats. The possible protective effects of selenium and vitamin E supplemented to rats housed in concrete-protected cages using hematite and colemanite were tested and compared to untreated controls. Ninety-six rats were randomly divided into four main equal groups namely control (A), normal concrete (B), concrete containing colemanite (C), and concrete containing hematite (D). Except group A, all groups exposed to 7 Gy radiation. The four main groups were divided into four subgroups each as follows: subgroups 1 (n = 6): nonpregnant control rats. Subgroups 2 (n = 6): selenium and vitamin E combination was intraperitoneally (i.p.) given to the nonpregnant rats for 20 days. Subgroups 3 (n = 6): pregnant control rats. Subgroups 4 (n = 6): selenium and vitamin E combination was i.p. given to the pregnant rats for concessive 20 days. Lactate dehydrogenate, alkaline phosphates, and lipid peroxidation values were higher in subgroups 1 and 3 than in no radiation group although glutathione peroxidase and vitamin E levels in liver were lower in radiation group than in no radiation group. Lactate dehydrogenate activity and lipid peroxidation levels were found to be decreased in subgroups 2 and 4 protected with concrete containing hematite and colemanite when compared to subgroup 1 and 3 with normal concrete. The radiation doses in rats housed by concrete without colemanite and hematite exposed radiation clearly showed liver degeneration. In conclusion, selenium and vitamin E supplementations and housing by concrete with colemanite was found to offer protection against gamma-irradiation-induced liver damage and oxidative stress in rats, probably by exerting a protective effect against liver necrosis via its free radical scavenging and membrane stabilizing. Protective effects of colemanite in the liver seem to be more important than in hematite. PMID:19763408
Gençel, Osman; Naziroglu, Mustafa; Celik, Omer; Yalman, Kadir; Bayram, Dilek
Fluoxetine administration to pregnant rats increases anxiety-related behavior in the offspring
Rationale Fluoxetine (Prozac®) is the most frequently prescribed drug to battle depression in pregnant women, but its safety in the\\u000a unborn child has not yet been established. Fluoxetine, a selective serotonin reuptake inhibitor, crosses the placenta, leading\\u000a to increased extracellular serotonin levels and potentially neurodevelopmental changes in the fetus.\\u000a \\u000a \\u000a \\u000a \\u000a Objectives The purpose of this study was to elucidate the long-term consequences of
Jocelien D. A. Olivier; A. Vallčs; Floor van Heesch; Anthonieke Afrasiab-Middelman; Janneke J. P. M. Roelofs; Marloes Jonkers; Elke Joan Peeters; Gerdien A. H. Korte-Bouws; Jos P. Dederen; Amanda J. Kiliaan; Gerard J. Martens; Dirk Schubert; Judith R. Homberg
Aldosterone metabolism in the isolated perfused liver of female and male rats
A sex-dependent metabolism of aldosterone has been reported in intact rats. To further characterize the hepatic elimination of aldosterone and its sex dependence, the metabolism of d-(4-14C)aldosterone was studied in isolated perfused liver from male and female Wistar rats, from male rats castrated 3 weeks before experiments, and from younger male rats (same body weight as the female rats). The livers were perfused at a constant flow rate in a recirculating mode with a hemoglobin-free medium containing aldosterone at initially 1 nM. Perfusate aldosterone was measured by a specific RIA. Total 4-14C radio-activity in perfusate and bile was determined. The perfusate (4-14C)aldosterone radiometabolite concentration was calculated. The radiometabolite pattern in additional experiments was studied by HPLC. The male rats exhibited 10% higher systolic blood pressure (P less than 0.05) and 51% higher fasting values of plasma aldosterone (P less than 0.05) compared to those in the female rats. In female rats the hepatic clearance rate of aldosterone per 100 g BW was 72% higher than that in male rats (11.2 +/- 2.7 to 6.5 +/- 1.8 ml/min: P less than 0.01), and that expressed per g liver wet wt was 75% higher (3.5 +/- 1.0 to 2.0 +/- 0.7 ml/min; P less than 0.01). When female rats were compared to younger male rats with the same body weight, 33% higher hepatic aldosterone clearance rates were still found in female rats (21.0 +/- 5.4 to 15.8 +/- 3.2 ml/min; P less than 0.05), and 51% higher values when expressed per g liver wet wt (3.5 +/- 1.0 to 2.3 +/- 0.5 ml/min; P less than 0.01). No difference in the aldosterone clearance rate was observed in castrated male rats compared to that in noncastrated male rats. 4-14C-Labeled radiometabolite levels accumulated similarly in the perfusate of livers of both sexes.
Egfjord, M.; Olgaard, K. (Rigshospitalet, Copenhagen (Denmark))
Serotonergic projections from the caudal raphe nuclei to the hypoglossal nucleus in male and female rats
The respiratory control system is sexually dimorphic. In many brain regions, including respiratory motor nuclei, serotonin (5HT) levels are higher in females than in males. We hypothesized that there could be sex differences in 5HT input to the hypoglossal nucleus, a region of the brainstem involved in upper airway control. Adult Fischer 344 rats were anesthetized and a retrograde transsynaptic neuroanatomical tracer, Bartha pseudorabies virus (PRV), was injected into the tongue. Sections through the medulla were reacted immunocytochemically for the presence of (i) PRV, (ii) tryptophan hydroxylase (TPH; marker of 5HT neurons), (iii) PRV combined with TPH, and (iv) 5HT. Sex hormone levels were measured in female rats and correlated with TPH immunoreactivity, as hypoglossal 5HT levels vary with the estrous cycle. The number of PRV neurons was comparable in male and female rats. The number and distribution of TPH immunoreactive neurons in the caudal raphe nuclei were similar in male and female rats. The subset of 5HT neurons that innervate hypoglossal motoneurons was also similar in male and female rats. With the exception of the ventrolateral region of the hypoglossal nucleus, 5HT immunoreactivity was similar in male and female rats. These data suggest that sex differences in 5HT modulation of hypoglossal motoneurons in male and female rats are not the result of sex differences in TPH or 5HT, but may result from differences in neurotransmitter release and reuptake, location of 5HT synaptic terminals on hypoglossal motoneurons, pre- and postsynaptic 5HT receptor expression, or the distribution of sex hormone receptors on hypoglossal or caudal raphe neurons.
Barker, Jessica R.; Thomas, Cathy F.; Behan, Mary
Pharmacokinetics and metabolism of SK&F 86002 in male and female Sprague-Dawley rats.
Several pharmacokinetic parameters for SK&F 86002 [6-(4'-fluorophenyl)-5-(4'-pyridyl)-2,3-dihydroimidazo(2,1-b)-thia zole] and its metabolites (sulfoxide, sulfone) were measured in male and female Sprague-Dawley rats after iv (5 mg/kg) and a wide range (10-80 mg/kg) of oral doses of SK&F 86002. In both sexes. SK&F 86002 is metabolized to an active metabolite, sulfone, which has an extended half-life (approximately 13 hr) and, therefore, has the potential to accumulate upon repeated dosing. In addition, striking differences between sexes were noted in several of the pharmacokinetic parameters measured. The AUCs areas under the plasma concentration time curves, for SK&F 86002 in female rats obtained at the higher doses of SK&F 86002 were substantially greater than expected, when compared with lower doses in female rats or with equivalent doses in male rats. Furthermore, at all doses of SK&F 86002, AUCs for sulfoxide were substantially larger in female than in male rats. Consequently, the systemic exposure to SK&F 86002 and metabolites is substantially greater in female rats than in male rats. Therefore, extrapolation of the pharmacologic and toxicologic sequelae of SK&F 86002, observed at larger doses in female rats, to lower doses should be approached cautiously. Furthermore, the extended half-life of the pharmacologically active sulfone metabolite of SK&F 86002 suggests that this metabolite could accumulate on repeated daily dosing of SK&F 86002 and could, therefore, account for much of the chronic pharmacologic and toxicologic activity of SK&F 86002. PMID:2565207
Newton, J F; Yodis, L P; Keohane, D; Eckardt, R; Dewey, R; Dent, J; Mico, B
4,4'-Methylenedianiline (4,4'-diaminodiphenylmethane; DAPM) is an aromatic diamine used in the production of numerous polyurethane foams and epoxy resins. Previous studies in rats revealed that DAPM initially injures biliary epithelial cells of the liver, that the toxicity is greater in female than in male rats, and that the toxic metabolites of DAPM are excreted into bile. Since male and female rats exhibit differences in the expression of both phase I and phase II enzymes, our hypothesis was that female rats either metabolize DAPM to more toxic metabolites or have a decreased capacity to conjugate metabolites to less toxic intermediates. Our objective was thus to isolate, characterize, and quantify DAPM metabolites excreted into bile in both male and female bile duct-cannulated Sprague Dawley rats. The rats were gavaged with [14C]-DAPM, and the collected bile was subjected to reversed-phase HPLC with radioisotope detection. Peaks eluting from HPLC were collected and analyzed using electrospray MS, NMR and FT-IR spectroscopy. HPLC analysis indicated numerous metabolites in both sexes, but male rats excreted greater amounts of glutathione and glucuronide conjugates than females. Electrospray MS and NMR spectra of HPLC fractions revealed that the most prominent metabolite found in bile of both sexes was a glutathione conjugate of an imine metabolite of a 4'-nitroso-DAPM. Seven other metabolites were identified, including acetylated, cysteinyl-glycine, glutamyl-cysteine, glycine, and glucuronide conjugates. While our prior studies demonstrated increased covalent binding of DAPM in the liver and bile of female compared to male rats, in these studies, SDS-PAGE with autoradiography revealed 4–5 radiolabeled protein bands in the bile of rats treated with [14C]-DAPM. In addition, these bands were much more prominent in female than in male rats. These studies thus suggest that a plausible mechanism for the increased sensitivity of female rats to DAPM toxicity may be decreased conjugation of reactive DAPM metabolites, leading to greater levels of protein adduct formation.
Chen, Kan; Cole, Richard B.; Cruz, Vicente Santa; Blakeney, Ernest W.; Kanz, Mary F.; Dugas, Tammy R.
Characterization of biliary conjugates of 4,4'-methylenedianiline in male versus female rats.
4,4'-Methylenedianiline (4,4'-diaminodiphenylmethane; DAPM) is an aromatic diamine used in the production of numerous polyurethane foams and epoxy resins. Previous studies in rats revealed that DAPM initially injures biliary epithelial cells of the liver, that the toxicity is greater in female than in male rats, and that the toxic metabolites of DAPM are excreted into bile. Since male and female rats exhibit differences in the expression of both phase I and phase II enzymes, our hypothesis was that female rats either metabolize DAPM to more toxic metabolites or have a decreased capacity to conjugate metabolites to less toxic intermediates. Our objective was thus to isolate, characterize, and quantify DAPM metabolites excreted into bile in both male and female bile duct-cannulated Sprague Dawley rats. The rats were gavaged with [(14)C]-DAPM, and the collected bile was subjected to reversed-phase HPLC with radioisotope detection. Peaks eluting from HPLC were collected and analyzed using electrospray MS and NMR spectroscopy. HPLC analysis indicated numerous metabolites in both sexes, but male rats excreted greater amounts of glutathione and glucuronide conjugates than females. Electrospray MS and NMR spectra of HPLC fractions revealed that the most prominent metabolite found in bile of both sexes was a glutathione conjugate of an imine metabolite of a 4'-nitroso-DAPM. Seven other metabolites were identified, including acetylated, cysteinyl-glycine, glutamyl-cysteine, glycine, and glucuronide conjugates. While our prior studies demonstrated increased covalent binding of DAPM in the liver and bile of female compared to male rats, in these studies, SDS-PAGE with autoradiography revealed 4-5 radiolabeled protein bands in the bile of rats treated with [(14)C]-DAPM. In addition, these bands were much more prominent in female than in male rats. These studies thus suggest that a plausible mechanism for the increased sensitivity of female rats to DAPM toxicity may be decreased conjugation of reactive DAPM metabolites, leading to greater levels of protein adduct formation. PMID:18692083
Chen, Kan; Cole, Richard B; Santa Cruz, Vicente; Blakeney, Ernest W; Kanz, Mary F; Dugas, Tammy R
Acute withdrawal but not long-term withdrawal from methamphetamine affects sexual behavior in female rats.
The present study was designed to investigate the long-term effects of repeated methamphetamine (MA) exposure on sexual motivation in female rats tested after a period of drug abstinence. In Experiment 1, female subjects received three injections of MA (1.0mg/kg/day, every other day) or saline and were tested for paced mating behavior (where females could control the receipt of sexual stimulation from one male rat) 21 days after their last injection. In Experiment 2, female subjects received 12 consecutive injections of MA (1.0mg/kg/day) or saline and were tested for mate choice (where females could control the receipt of sexual stimulation from two male rats simultaneously) 6 days after their last injection. Experiment 3 was identical to Experiment 2 except that female subjects received no baseline mating test and were tested for mate choice 24h and 6 days after their last injection. Open field tests were conducted in each experiment to measure locomotor activity after repeated exposure to MA. Although repeated MA exposure increased locomotor activity, mating behavior was not facilitated after either a short (6 days) or long (21 days) period of drug abstinence. Nevertheless, sexual behavior was disrupted during the 24h acute withdrawal period. Therefore, although the present study found no evidence of cross-sensitization between female sexual behavior and MA after either a short or a long period of drug abstinence, sexual behavior in sexually naďve female rats is sensitive to the depressive state associated with acute withdrawal from MA. In conclusion, the results of the present study suggest that MA acts differently from other psychomotor stimulants, and that the effects of MA withdrawal on sexual behavior differ between male and female rats. PMID:23268346
Thibodeau, Rachel B; Ornelas, Laura C; Romero, Jordan; Memos, Nicoletta; Scheible, Matthew; Avila, Alfred; Schumacher, Abby; Navarro, April; Zimmermann, Karen; Cuenod, Bethany A; Frohardt, Russell J; Guarraci, Fay A
Physiologically based pharmacokinetic modeling of the pregnant rat: A multiroute exposure model for trichloroethylene and its metabolite, trichloroacetic acid. (Reannouncement with new availability information). Interim report, April 1986-December 1988
A physiologically based pharmacokinetic (PB-PK) model was developed to describe trichloroethylene (TCE) kinetics in the pregnant rat exposed to TCE by inhalation, by bolus gavage, or by oral ingestion in drinking water. The kinetics of trichloroacetic acid (TCA), an oxidative metabolite of TCE, were described by a classical one-compartment pharmacokinetic model. Among the required model parameters for TCE, partition coefficients (PCs) and kinetic constants for oxidation were determined by vial equilibration and gas uptake methods, respectively. The fat:blood PC was 33.9; the blood:air PC was 13.2; and the fetal tissue:fetal blood PC was 0.51. TCE was readily metabolized with high substrate affinity. In naive and pregnant female rats the maximum velocities of oxidative metabolism were 10.98 + 0.155 and 9.18 +/- 0.078 mg/kg/hr, while the estimated Michaelis constant for the two groups of rats was very low, 0.25 mg/liter. The first-order rate constant for oral absorption of TCE from water was 5.4 +/- 0.42/hr-1 in naive rats. With TCA, the volume of distribution (0.618 liter/kg) and the plasma elimination rate constant (0-045 0.0024/hour) were estimated both from intravenous dosing studies with TCA and from an inhalation study with TCE. By comparison of the two routes of administration, the stoichiometric yield of TCA from Pregnancy, Physiologically Based Pharmacokinetic Modeling, Toxicology, Trichloroethylene, Trichloroacetic Acid.
Fisher, J.W.; Whittaker, T.A.; Taylor, D.H.; Clewell, H.J.; Andersen, M.E.
17?-estradiol is necessary for extinction of cocaine seeking in female rats.
Human and preclinical models of addiction demonstrate that gonadal hormones modulate acquisition of drug seeking. Little is known, however, about the effects of these hormones on extinction of drug-seeking behavior. Here, we investigated how 17?-estradiol (E?) affects expression and extinction of cocaine seeking in female rats. Using a conditioned place preference (CPP) paradigm, ovariectomized rats were maintained throughout conditioning with 2 d of E? treatment followed by 2 d of vehicle treatment, or were injected with E? daily. Hormone injections were paired or explicitly unpaired with place conditioning sessions. Expression of a cocaine CPP was of equal magnitude regardless of conditioning protocol, suggesting that E? levels during conditioning did not affect subsequent CPP expression. During extinction, daily E? administration initially enhanced expression of the cocaine CPP, but resulted in significantly faster extinction compared to controls. Whereas E?-treated rats were extinguished within 8 d, vehicle-treated rats maintained CPP expression for more than a month, indicative of perseveration. To determine whether E? could rescue extinction in these rats, half were given daily E? treatment and half were given vehicle. E?-treated rats showed rapid extinction, whereas vehicle-treated rats continued to perseverate. These data demonstrate for the first time that E? is necessary for extinction of cocaine seeking in female rats, and that it promotes rapid extinction when administered daily. Clinically, these findings suggest that monitoring and maintaining optimal E? levels during exposure therapy would facilitate therapeutic interventions for female cocaine addicts. PMID:23676202
Twining, Robert C; Tuscher, Jennifer J; Doncheck, Elizabeth M; Frick, Karyn M; Mueller, Devin
Paradoxical sleep deprivation in female rats alters drug-induced behaviors.
Paradoxical sleep deprivation (PSD) induces changes in behaviors induced by dopaminergic and cholinergic agonists, including increased aggressive behavior and stereotypy, decreased number of yawns, and shedding of bloody tears in male rats. In female rats, however, very little is known about the relationship between PSD and the effect of these drugs. The present study sought to examine this issue. As in males, PSD in females resulted in increased apomorphine-induced stereotypy, decreased pilocarpine-induced chromodacryorrhea, and hyperthermia. Unlike males, however, no apomorphine-induced aggressiveness or apomorphine- and pilocarpine-induced yawning were observed in PSD females. These findings suggest that female sexual hormones may affect the expression of some behaviors and not the neurotransmission as a whole, because drug-induced behaviors in PSD females were partly similar to those observed in PSD males. PMID:7652035
Hipólide, D C; Tufik, S
Long-term programming of enhanced aggression by peripuberty stress in female rats.
Human literature has linked adverse early life experiences with an increased risk to develop violent behaviors in both boys and girls. We have previously shown that male rats submitted to stress during the peripuberty period display as adults abnormal aggressive behavior against both male intruders and female partners. In the present study, we examined whether the same stress protocol would affect the development of aggressive behaviors in female rats. We evaluated the behavior of these peripuberty stressed female rats when confronted, at adulthood, with either female or male intruders, and during their cohabitation with male partners. Given that estrus cycle influences mood and aggressive behaviors, female aggressive behavior was assessed at different estrus cycle phases: estrus and diestrus, and during pregnancy and lactancy. Additionally, we evaluated postpartum plasma levels of vasopressin, oxytocin and corticosterone, hormones associated with aggression and the regulation of social behavior. Compared to control females, females submitted to stressful events during puberty exhibited higher and more sustained rates of aggression during adulthood independently on the estrus cycle or the sex of the intruder, and they had higher levels of plasma vasopressin. Significant correlations between plasma levels of vasopressin and corticosterone and aggressive behavior were also found. Strikingly, our results showed opposite intragroup correlations suggesting a different role of these hormones on aggression depending on life experiences. We provide here an animal model, devoid of cultural influences strongly supporting a role for biological factors in the development of aggressive behaviors following exposure to stressful events at puberty in females. PMID:23942011
Cordero, M Isabel; Ansermet, François; Sandi, Carmen
Metabolism and physiologically based pharmacokinetic modeling of flumioxazin in pregnant animals.
A physiologically based pharmacokinetic (PBPK) model was developed to predict the concentration of flumioxazin, in the blood and fetus of pregnant humans during a theoretical accidental intake (1000mg/kg). The data on flumioxazin concentration in pregnant rats (30mg/kg po) was used to develop the PBPK model in pregnant rats using physiological parameters and chemical specific parameters. The rat PBPK model developed was extrapolated to a human model. Liver microsomes of female rats and a mixed gender of humans were used for the in vitro metabolism study. To determine the % of flumioxazin absorbed after administration at a dose of 1000mg/kg assuming maximum accidental intake, the biliary excretion study of [phenyl-U-(14)C]flumioxazin was conducted in bile duct-cannulated female rats (Crl:CD (SD)) to collect and analyze the bile, urine, feces, gastrointestinal tract, and residual carcass. The % of flumioxazin absorbed at a dose of 1000mg/kg in rats was low (12.3%) by summing up (14)C of the urine, bile, and residual carcass. The pregnant human model that was developed demonstrated that the maximum flumioxazin concentration in the blood and fetus of a pregnant human at a dose of 1000mg/kg po was 0.86?g/mL and 0.68?g/mL, respectively, which is much lower than Km (202.4?g/mL). Because the metabolism was not saturated and the absorption rate was low at a dose of 1000mg/kg, the calculated flumioxazin concentration in pregnant humans was thought to be relatively low, considering the flumioxazin concentration in pregnant rats at a dose of 30mg/kg. For the safety assessment of flumioxazin, these results would be useful for further in vitro toxicology experiments. PMID:24717917
Takaku, Tomoyuki; Nagahori, Hirohisa; Sogame, Yoshihisa
Effects of prenatal administration of testosterone and cortisone on the reproductive system of the female rat.
Testosterone propionate, cortisone, or sesame oil vehicle were given to rats during the last week of pregnancy so that effects of the hormones on anogenital distance, breeding capacity and vaginal opening of the female progeny could be contrasted. Testosterone significantly increased anogenital distance and delayed vaginal opening of progeny. When females that had been exposed to testosterone in utero were tested for breeding capacity, a significantly smaller number mated than in the control group. Female rats that had been exposed to cortisone in utero exhibited premature vaginal opening but did not differ from controls in anogenital distance, and, unlike the testosterone-exposed rats, mated. Cortisone-exposed rats carried litters to term and the litters did not differ from those of controls in numbers of pups or numbers of living pups at birth. The pups born to cortisone-exposed rats had greater birth weights and a higher survival rate to 20 days of age than pups of controls. Results indicate that testosterone administration to rats during pregnancy is far more detrimental to the development and subsequent function of the reproductive system of female progeny than cortisone and suggest that similar changes which occur in response to maternal stress or to administration of ACTH during pregnancy are more likely to result from increases in testosterone than from increases in glucocorticoid secretion. PMID:1740970
McCoy, S J; Shirley, B A
Prenatal choline availability modulates hippocampal neurogenesis and neurogenic responses to enriching experiences in adult female rats
Increased dietary intake of choline early in life improves performance of adult rats on memory tasks and prevents their age-related memory decline. Because neurogenesis in the adult hippocampus also declines with age, we investigated whether prenatal choline availability affects hippocampal neurogenesis in adult Sprague–Dawley rats and modifies their neurogenic response to environmental stimulation. On embryonic days (ED) 12?17, pregnant rats ate a choline-supplemented (SUP-5 g/kg), choline sufficient (SFF-1.1 g/kg), or choline-free (DEF) semisynthetic diet. Adult offspring either remained in standard housing or were given 21 daily visits to explore a maze. On the last ten exploration days, all rats received daily injections of 5-bromo-2-deoxyuridine (BrdU, 100 mg/kg). The number of BrdU+ cells was significantly greater in the dentate gyrus in SUP rats compared to SFF or DEF rats. While maze experience increased the number of BrdU+ cells in SFF rats to the level seen in the SUP rats, this enriching experience did not alter cell proliferation in DEF rats. Similar patterns of cell proliferation were obtained with immunohistochemical staining for neuronal marker doublecortin, confirming that diet and exploration affected hippocampal neurogenesis. Moreover, hippocampal levels of the brain-derived neurotrophic factor (BDNF) were increased in SUP rats as compared to SFF and DEF animals. We conclude that prenatal choline intake has enduring effects on adult hippocampal neurogenesis, possibly via up-regulation of BDNF levels, and suggest that these alterations of neurogenesis may contribute to the mechanism of life-long changes in cognitive function governed by the availability of choline during gestation.
Glenn, Melissa J.; Gibson, Erin M.; Kirby, Elizabeth D.; Mellott, Tiffany J.; Blusztajn, Jan K.; Williams, Christina L.
Development of multi-route physiologically-based pharmacokinetic models for ethanol in the adult, pregnant, and neonatal rat.
Biofuel blends of 10% ethanol (EtOH) and gasoline are common in the USA, and higher EtOH concentrations are being considered (15-85%). Currently, no physiologically-based pharmacokinetic (PBPK) models are available to describe the kinetics of EtOH-based biofuels. PBPK models were developed to describe life-stage differences in the kinetics of EtOH alone in adult, pregnant, and neonatal rats for inhalation, oral, and intravenous routes of exposure, using data available in the open literature. Whereas ample data exist from gavage and intravenous routes of exposure, kinetic data from inhalation exposures are limited, particularly at concentrations producing blood and target tissue concentrations associated with developmental neurotoxicity. Compared to available data, the three models reported in this paper accurately predicted the kinetics of EtOH, including the absorption, peak concentration, and clearance across multiple datasets. In general, model predictions for adult and pregnant animals matched inhalation and intravenous datasets better than gavage data. The adult model was initially better able to predict the time-course of blood concentrations than was the neonatal model. However, after accounting for age-related changes in gastric uptake using the calibrated neonate model, simulations consistently reproduced the early kinetic behavior in blood. This work provides comprehensive multi-route life-stage models of EtOH pharmacokinetics and represents a first step in development of models for use with gasoline-EtOH blends, with additional potential applicability in investigation of the pharmacokinetics of EtOH abuse, addiction, and toxicity. PMID:22954395
Martin, Sheppard A; McLanahan, Eva D; El-Masri, Hisham; LeFew, William R; Bushnell, Philip J; Boyes, William K; Choi, Kyoungju; Clewell, Harvey J; Campbell, Jerry L
Perinatal exposure of female rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin induces central precocious puberty in the offspring.
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during the fetal and neonatal periods has been indicated to alter the development of the offspring later in life. In this study, we determined whether perinatal exposure to a low dose of TCDD affects the onset of puberty in the female offspring of Long-Evans hooded rats. On day 15 of gestation, pregnant female rats were administered TCDD by gavage at a single dose of 0 (vehicle), 200, or 800 ng/kg b.w. In the female offspring born to dams administered with TCDD at either 200 or 800 ng/kg b.w., the vaginal opening and first estrus occurred approximately 4-7 days earlier than in the offspring born to vehicle-treated animals. The ovarian weight gain was also accelerated following exposure to TCDD in a dose-dependent manner. We next examined the ovarian compensatory hypertrophy (OCH) as an indicator of the maturation of the LH/GnRH-generating system in the pituitary and the hypothalamus. Exposure to TCDD accelerated the onset of OCH in the female offspring in a dose-dependent manner. In particular, in the offspring born to the dams exposed to TCDD at 800 ng/kg b.w., hypertrophy, which is characterized by hyperovulation and a marked increase in the weight of the remaining ovary after hemi-ovariectomy, was observed on postnatal days 27-30, which was 10 days earlier than in the offspring born to the vehicle-treated dams. These results indicate that perinatal exposure to a low dose of TCDD induces precocious puberty, including early maturation of the hypothalamic-pituitary axis, the gonads and genitals, in female Long-Evans hooded rats. PMID:18434365
Kakeyama, Masaki; Sone, Hideko; Tohyama, Chiharu
Pivalate lowers litter sizes and weights in female rats independent of its effect on carnitine status.
The present study investigated whether treatment of female rats with pivalate affects their reproductive function. Therefore, two experiments with female rats were performed. The first experiment included two groups of rats which received drinking water without (control) or with 20 mmol pivalate/L. The second experiment included a control group (which received drinking water without pivalate and a diet without added carnitine) and four groups which received drinking water with 20 mmol/L pivalate and diets without or with 1, 3 or 5 g added carnitine/kg, respectively. In both experiments, rats treated with pivalate had a lower number of pups born alive and, as a consequence of this, lower litter weights than control rats (p<0.05); pup weights were not altered by pivalate treatment. Supplementation of dietary carnitine in Experiment 2 increased plasma and tissue carnitine concentration even in excess of those in control rats but did not restore normal litter sizes. This study shows for the first time that pivalate affects the reproductive function in female rats independent of its effect on the carnitine status. PMID:17482425
Doberenz, Jane; Hirche, Frank; Keller, Uta; Eder, Klaus
Differential effects of chronic unpredictable stress on hippocampal CB1 receptors in male and female rats
Chronic unpredictable mild stress (CMS), an animal model of depression, downregulates hippocampal CB1 receptors in adult male rats. Given that endocannabinoids are implicated in modulating stress and anxiety and that women are vulnerable to stress-related disorders, we tested the effects of CMS on both female and male rats. Gonadectomized (gndx) and gonadally intact male and female rats were exposed to a three-week chronic stress protocol. Following CMS, CB1 receptor and fatty-acid-amide-hydrolase (FAAH) expression levels in the hippocampus were assessed by western blot analysis. CMS reliably produced a downregulation of CB1 receptors (?50%) in the hippocampus of both gndx and intact males. This effect was more robust in the dorsal than in the ventral hippocampus. Conversely, CMS produced an upregulation of CB1 receptors (?150%) in the hippocampus of both gndx and intact females. This upregulation was only observed in the dorsal hippocampus of female animals. CMS produced an upregulation of FAAH levels in both male and female animals. In non-stress control animals, males were observed to have higher CB1 levels than females, but no differences in FAAH were found. These findings suggest that the endocannabinoid (eCB) system is preferentially organized in male and female animals to respond differentially to chronic stress. These sex differences in the eCB system may help development of novel treatments for stress and depression that are designed specifically for women and men.
Reich, Christian G.; Taylor, Michael E.; McCarthy, Margaret M.
Chronic social instability stress in female rats: A potential animal model for female depression
Epidemiological studies demonstrate that affective disorders are at least twice as common in women as in men, but surprisingly, very few preclinical studies have been conducted on female experimental animals. Therefore, the necessity of developing valid animal models for studying the pathophysiology of stress-related disorders in women is obvious. Chronic social stress has the potential to induce depression in humans
C. J. Herzog; B. Czéh; S. Corbach; W. Wuttke; O. Schulte-Herbrüggen; R. Hellweg; G. Flügge; E. Fuchs
Inflammatory processes enhance cAMP-mediated uterus relaxation in the pregnant rat: the role of TNF-alpha.
The objective of this study was to assess the in vitro uterus relaxing potency of beta(2)-adrenergic receptor (beta(2)-AR) agonists in pregnant rats after in utero administration of the bacterial lipopolysaccharide, Escherichia coli endotoxin (LPS). The LPS (100 microg/kg) was injected into the uterine lumen on day 16 of pregnancy. The effects of beta(2)-AR agonist terbutaline was tested in vitro, in isolated uterine rings precontracted by electric field stimulation. Uterine beta(2)-AR densities were detected by radioligand binding assay, the activated G-protein levels were investigated by a radiolabelled GTP binding assay. Uterine cAMP accumulation and the serum tumor necrosis factor-alpha (TNF-alpha) levels were measured by enzyme immunoassay. The endotoxin-evoked preterm delivery occurred on day 21. Higher pD(2) values of terbutaline (p < 0.001) were detected in endotoxin-treated rats: 9.14 +/- 0.36 vs. 7.71 +/- 0.12 compared with sham-operated rats. The densities or the equilibrium dissociation constants of beta(2)-ARs were not different (p > 0.05) in LPS-treated vs. control animals. Serum TNF-alpha level rose threefold after LPS treatment, but this rise was abolished by thalidomide. In LPS + thalidomide-treated rats, the effect of terbutaline became similar to that in sham-operated controls. By the measurement of myometrial cAMP levels, we documented that the concentration-response curve of terbutaline on cAMP accumulation was shifted to the left in the LPS-treated rats, with a significant rise in the pD(2). We concluded that in the case of uterine inflammation, the in vitro uterus-relaxing potency of beta(2)-agonists enhances, which is possibly mediated by TNF-alpha and uterine cAMP levels and that may serve as a rationale for the use of beta(2)-AR agonists in the attenuation of preterm uterine contractions on an inflammatory basis. PMID:19050852
Klukovits, Anna; Márki, Arpád; Páldy, Eszter; Benyhe, Sándor; Gálik, Márta; Falkay, George; Gáspár, Róbert
Cognitive differences between male and female rats following exposure to 56Fe particles
NASA Astrophysics Data System (ADS)
On exploratory class missions astronauts will be exposed to types and doses of radiation (HZE particles) that are not experienced in low earth orbit. While it is likely that the crew will consist of both male and female astronauts, there has been little research on the effects of exposure to HZE particles on cognitive performance in female subjects. While previous research has shown that exposure to HZE particles disrupts cognitive performance in male rats it remains to be established whether or not similar effects will occur with female subjects because estrogen may act as a neuroprotectant. Ovariectomized (OVX) female rats were obtained from Taconic Farms. Thirty mm segments of silastic tubing containing either 180 pg l7-estradiol/mL in sesame oil or vehicle alone were implanted subcutaneously in the neck. Three days following surgery the rats were exposed to 56Fe particles (1000 MeV/n, 0-200 cGy) at the NSRL. Following irradiation the rats were shipped to UMBC for behavioral testing. The results indicated that the pattern of decrements in cognitive performance differed between male and female rats. In addition, for female rats, there were differences in performance as a function of the presence or absence of estradiol. In the vehicle implanted subjects exposure to 56Fe particles did not affect operant responding on an ascending fixed-ratio schedule; whereas irradiation did disrupt responding in OVX animals given estradiol. These results suggest that estrogen may not be protective following exposure to HZE particles. This research was supported by Grant NNX08AM66G from NASA.
Rabin, Bernard; Shukitt-Hale, Barbara; Carrihill-Knoll, Kirsty; Luskin, Katharine; Long, Lauren; Joseph, James
Angiotensin type 2 receptor stimulation increases renal function in female, but not male, spontaneously hypertensive rats.
Accumulating evidence suggests that the protective pathways of the renin-angiotensin system are enhanced in women, including the angiotensin type 2 receptor (AT2R), which mediates vasodilatory and natriuretic effects. To provide insight into the sex-specific ability of pharmacological AT2R stimulation to modulate renal function in hypertension, we examined the influence of the AT2R agonist, compound 21 (100-300 ng/kg per minute), on renal function in 18- to 19-week-old anesthetized male and female spontaneously hypertensive rats. AT2R stimulation significantly increased renal blood flow in female hypertensive rats (PTreatment<0.001), without influencing arterial pressure. For example, at 300 ng/kg per minute of compound 21, renal blood flow increased by 14.3±1.8% from baseline. Furthermore, at 300 ng/kg per minute of compound 21, a significant increase in urinary sodium excretion was observed in female hypertensive rats (+180±59% from baseline; P<0.05 versus vehicle-treated rats). This was seen in the absence of any major change in glomerular filtration rate, indicating that the natriuretic effects of AT2R stimulation were likely the result of altered renal tubular function. Conversely, we did not observe any significant effect of AT2R stimulation on renal hemodynamic or excretory function in male hypertensive rats. Finally, gene expression studies confirmed greater renal AT2R expression in female than in male hypertensive rats. Taken together, acute AT2R stimulation enhanced renal vasodilatation and sodium excretion without concomitant alterations in glomerular filtration rate in female hypertensive rats. Chronic studies of AT2R agonist therapy on renal function and arterial pressure in hypertensive states are now required to establish the suitability of AT2R as a therapeutic target for cardiovascular disease, particularly in women. PMID:24842923
Hilliard, Lucinda M; Chow, Charis L E; Mirabito, Katrina M; Steckelings, U Muscha; Unger, Thomas; Widdop, Robert E; Denton, Kate M
Measurement of Toluene Concentrations in the Blood of Fetuses of Pregnant Rats Exposed to Low Concentration Toluene Using Headspace-Solid Phase Micro Extraction-Gas Chromatography-Mass Spectrometry
In order to measure the level of toluene in the blood of fetuses of pregnant rats exposed to toluene, application of headspace-solid phase micro extraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) was studied. Pregnant rats from gestational day 15 (GD15) to GD19 were subjected to inhalational exposure to toluene for 90 min per day. They were obtained by Cesarean section on the fifth
Daisuke Nakajima; Shinji Tsukahara; Rieko Hojo; Shiho Kageyama; Sumio Goto; Hiroaki Shiraishi; Fujio Shiraishi; Hidekazu Fujimakia
Correlative Analysis of Behavioral and Physiological Concomitants of Labor in Pregnant Rats
NASA Technical Reports Server (NTRS)
During parturition, rats exhibit characteristic behavioral expressions of labor. Lordosis contractions, consisting of an elongation of the dams body, are observed beginning several hours prior to neonate births, whereas vertical contractions, repeated rapid lifts of the abdomen, occur immediately preceding the birth of each neonate. We analyzed underlying changes in intrauterine pressure (IUP) using a telemetric sensor that we modified for use in freely-moving rats. This technique enabled us to correlate behavioral expressions of labor contractions with IUP. A small telemetric blood pressure sensor was fitted within a fluid-filled balloon, similar in size to a full term rat fetus. On Gestational day 19 of the rats' 22-day pregnancy, a unit was surgically implanted within the uterus. The dams were simultaneously videotaped, enabling us to directly correlate IUP signals with behavioral expressions of labor contractions. Earlier phases of labor, consisting predominantly of lordosis contractions were characterized by lower pressures relative to later phases during which higher pressures and vertical contractions were frequently observed.
Baer, L. A.; Wade, C. E.; Ronca, A. E.; Dalton, Bonnie (Technical Monitor)
Effects of Hypergravity Exposure On Plasma Oxytocin Concentrations In Pregnant and Lactating Rat Dams.
National Technical Information Service (NTIS)
Rat dams and offspring were exposed to 1.5-g, 1.75-g or 2.0-g hypergravity (hg) from Gestational day (G) 11 until Postnatal day (P) 10. To ascertain the role of maternal factors in reduced postnatal body weights of offspring developed in hg, the dams' lac...
L. A. Baer C. E. Wade A. E. Ronca
[Adrenalectomy changes diazepam performance in male and female rats under multiparametric test conditions].
It is established that adrenalectomy decreases the "sedative" and "anti-anxiety" effects and reduces the "anxiogenic" effect of diazepam in male rats under multiparametric test conditions. At the same time, the "sedative" and "activating" effects of this tranquilizer do not appear in adrenalectomized female rats and the "anti-anxiety" effect is only observed in the evening. The "anxiogenic" effect of diazepam in females is not observed for a drug dose of 0.5 mg/kg and is only manifested at a dose of 0.1 mg/kg. PMID:23762981
Manvelian, É A; Baturin, V A; Anisimova, N A
Serotonin 1A receptors and sexual behavior in female rats: a review.
This review focuses on the role of serotonin and especially 5-HT?A receptors in female rat sexual behavior. In addition, the differences and/or similarities with male rats are discussed. Overall, in both males and females 5-HT?A receptors do not appear to be involved in sexual behavior under normal circumstances, but become very important under conditions of elevated serotonin levels. 5-HT?A receptor agonists facilitate sexual behavior in male rats, but inhibit female sexual activity. At first sight, this seems quite conflicting, but could be due to our definitions of different elements of sexual behavior. Three different phases can be distinguished in rats' sexual cycle, the introductory (precopulatory), the copulatory and the executive (ejaculatory) phases. Different mechanisms and brain regions are involved in these phases. If the appropriate phases of males and females are properly compared, the role of 5-HT?A receptors in rats might be more similar than assumed thus far. PMID:24275184
Snoeren, Eelke M S; Veening, Jan G; Olivier, Berend; Oosting, Ronald S
Ventilation and phrenic output following high cervical spinal hemisection in male vs. female rats
Female sex hormones influence the neural control of breathing and may impact neurologic recovery from spinal cord injury. We hypothesized that respiratory recovery after C2 spinal hemisection (C2HS) differs between males and females and is blunted by prior ovariectomy (OVX) in females. Inspiratory tidal volume (VT), frequency (fR), and ventilation (VE) were quantified during quiet breathing (baseline) and 7% CO2 challenge before and after C2HS in unanesthetized adult rats via plethysmography. Baseline breathing was similarly altered in all rats (reduced VT, elevated fR) but during hypercapnia females had relatively higher VT (i.e. compared to pre-injury) than male or OVX rats (p < 0.05). Phrenic neurograms recorded in anesthetized rats indicated that normalized burst amplitude recorded ipsilateral to C2HS (i.e. the crossed phrenic phenomenon) is greater in females during respiratory challenge (p < 0.05 vs. male and OVX). We conclude that sex differences in recovery of VT and phrenic output are present at 2 weeks post-C2HS. These differences are consistent with the hypothesis that ovarian sex hormones influence respiratory recovery after cervical spinal cord injury.
Doperalski, N.J.; Sandhu, M.S.; Bavis, R.W.; Reier, P.J.; Fuller, D.D.
Reduction of extinction and reinstatement of cocaine seeking by wheel running in female rats
Rationale and objectives Previous work has shown that wheel running reduced the maintenance of cocaine self-administration in rats. In the present\\u000a study, the effect of wheel running on extinction and reinstatement of cocaine seeking was examined. Female rats were trained\\u000a to run in a wheel during 6-h sessions, and they were then catheterized and placed in an operant conditioning chamber where
Natalie E. Zlebnik; Justin J. Anker; Luke A. Gliddon; Marilyn E. Carroll
Perinatal Exposure to the Estrogenic Pollutant Bisphenol A Affects Behavior in Male and Female Rats
FARABOLLINI F., S. PORRINI, AND F. DESSĚ-FULGHERI. Perinatal exposure to the estrogenic pollutant Bisphenol A affects behavior in male and female rats. PHARMACOL BIOCHEM BEHAV 64(4) 687–694, 1999.—Bisphenol A (BPA) is an environmental estrogen with potentially aversive effects on public health. In rats, we studied the effects of perinatal exposure to BPA on nonsocial behaviors partly influenced by gonadal hormones.
F Farabollini; S Porrini
Effects of ethanol consumption by adult female rats on subsequent consumption by adolescents
We used a two-bottle choice test to measure voluntary ethanol consumption by adolescent rats that had lived with ethanol-consuming or water-consuming adult conspecifics. We found that housing weanlings with either a virgin or a lactating adult female rat that ingested ethanol increased the weanlings' subsequent voluntary intake of ethanol when they were fluid-deprived and provided with choices between 8% ethanol
P. Lynne Honey; Kevin R Varley; Bennett G Galef
Correction of Endothelial Dysfunction in Diabetic Female Rats by Tetrahydrobiopterin and Chronic Insulin
Diabetes-induced vascular dysfunction has mainly been studied in males. However, the mechanisms involved may not correspond to those in females. Here we analyzed the effects of tetrahydrobiopterin (BH4) and chronic insulin on the physiology of mesenteric arterioles of alloxan-diabetic female rats. The parameters studied were the mesenteric arteriolar reactivity (intravital microscopy), nitric oxide synthase (NOS) activity (conversion of L-arginine to
Eliana H. Akamine; Elisa M. Kawamoto; Cristoforo Scavone; Dorothy Nigro; Maria Helena C. Carvalho; Rita de Cássia A. Tostes; Luiz R. G. Britto; Zuleica B. Fortes
Estrogen deposits extra mineral into bones of female rats in puberty, but simultaneously seems to suppress the responsiveness of female skeleton to mechanical loading
To first test the possible effect of gender on the responsiveness of growing rat skeleton to mechanical loading, 5-week-old littermates of 25 male and 25 female rats were subjected to either free-cage activity or treadmill training for a period of 14 weeks (experiment 1). Using peripheral quantitative computed tomography (pQCT) and mechanical testing of the femoral neck, we observed female
T. L. N Järvinen; P Kannus; I Pajamäki; T Vuohelainen; J Tuukkanen; M Järvinen; H Sievänen
Infertility is a term doctors use if a woman hasn't been able to get pregnant after ... woman keeps having miscarriages, it is also called infertility. Female infertility can result from physical problems, hormone ...
Estrogen suppresses brain mitochondrial oxidative stress in female and male rats.
Mitochondria are a major source of reactive oxygen species (ROS) and oxidative stress, key contributors to aging and neurodegenerative disorders. We report that gonadal hormones influence brain mitochondrial ROS production in both females and males. Initial experiments showed that estrogen decreases mitochondrial superoxide production in a receptor-mediated manner, as measured by MitoSOX fluorescence in differentiated PC-12 cells. We then assessed in vivo effects of gonadal hormones on brain mitochondrial oxidative stress in female and male rats. Brain mitochondria were isolated to measure a functional indicator of ROS, i.e., activity of the ROS-sensitive mitochondrial enzyme, aconitase. Gonadectomy of both males and females caused a decrease in aconitase activity, suggesting that endogenous gonadal hormones influence mitochondrial ROS production in the brain. In vivo treatment of gonadectomized animals with testosterone or dihydrotestosterone (DHT) had no effect, but estrogen replacement significantly increased aconitase activity in brain mitochondria from both female and male rats. This indicates that estrogen decreases brain mitochondrial ROS production in vivo. Sex hormone treatments did not affect protein levels of brain mitochondrial uncoupling proteins (UCP-2, 4, and 5). However, estrogen did increase the activity, but not the levels, of manganese superoxide dismutase (MnSOD), the mitochondrial enzyme that catalyzes superoxide radical breakdown, in brain mitochondria from both female and male rats. Thus, in contrast to the lack of effect of androgens on mitochondrial ROS, estrogen suppression of mitochondrial oxidative stress may influence neurological disease incidence and progression in both females and males. PMID:17889838
Razmara, Ali; Duckles, Sue P; Krause, Diana N; Procaccio, Vincent
Estrogen Suppresses Brain Mitochondrial Oxidative Stress in Female and Male Rats
Mitochondria are a major source of reactive oxygen species (ROS) and oxidative stress, key contributors to aging and neurodegenerative disorders. We report that gonadal hormones influence brain mitochondrial ROS production in both females and males. Initial experiments showed that estrogen decreases mitochondrial superoxide production in a receptor-mediated manner, as measured by MitoSOX fluorescence in differentiated PC-12 cells. We then assessed in vivo effects of gonadal hormones on brain mitochondrial oxidative stress in female and male rats. Brain mitochondria were isolated to measure a functional indicator of ROS, i.e., activity of the ROS-sensitive mitochondrial enzyme, aconitase. Gonadectomy of both males and females caused a decrease in aconitase activity, suggesting endogenous gonadal hormones influence mitochondrial ROS production in the brain. In vivo treatment of gonadectomized animals with testosterone or dihydrotestosterone (DHT) had no effect, but estrogen replacement significantly increased aconitase activity in brain mitochondria from both female and male rats. This indicates estrogen decreases brain mitochondrial ROS production in vivo. Sex hormone treatments did not affect protein levels of brain mitochondrial uncoupling proteins (UCP-2, 4, and 5). However, estrogen did increase the activity, but not the levels, of manganese superoxide dismutase (MnSOD), the mitochondrial enzyme that catalyzes superoxide radical breakdown, in brain mitochondria from both female and male rats. Thus, in contrast to the lack of effect of androgens on mitochondrial ROS, estrogen suppression of mitochondrial oxidative stress may influence neurological disease incidence and progression in both females and males.
Razmara, Ali; Duckles, Sue P.; Krause, Diana N.; Procaccio, Vincent
Biometric and morphologic studies of the female reproductive organs of the African giant rat (Cricetomys gambianus: Waterhouse).
Different segments of the reproductive tract of 100 adult, non-pregnant, female African giant rats (AGR) were carefully examined, weighed, and measured. The ovaries were observed to be small, pinkish, and kidney-shaped. The uterus of the AGR was found to be uterus duplex. The live weight of the AGR was 999.7 ± 16.86 g. The weight, length, and width of the ovary were 0.095 ± 0.003 g, 0.750 ± 0.01 cm, and 0.01± 0.02 cm, respectively. The length of the oviduct, uterus, and vagina/vestibule were 4.44 ± 0.06 cm, 4.877 ± 0.11 cm, and 4.345 ± 0.07 cm, respectively. The weight and length of the entire tubular organs were 3.171 ± 0.01 g and 13.559 ± 0.18 cm with corresponding range values of 1.61-7.10 g and 7.80-17.40 cm, respectively. PMID:21120807
Ali, M N; Onyeanusi, B I; Ojo, S A; Ayo, J O; Maidawa, S M; Imam, J
Influence of male-related stimuli on female postejaculatory refractory period in rats.
Female rats "pace" their sexual contacts with the male when tested in situations where they can escape from the male during copulation. The type and quality of vaginocervical stimulation that the females receive during copulation influences their pacing behavior. This study investigated the effect of several male-related stimuli on the female's postejaculatory refractory period (PER). Females were tested in a two-compartment test chamber from which they could escape the male through one of four openings along the bottom of the barrier separating the two compartments. Experiment 1 examined the influence of the seminal plug, the penile cup, and prostate secretions on the female's PER. Results showed that neither the seminal plug, the penile cup, nor prostate secretions contributed to the female's PER. Experiment 2 investigated the relation of pre-ejaculatory intromission frequency, ejaculation duration, and the number of pelvic thrusts during ejaculation to the female's PER. Results indicated that pre-ejaculatory intromission frequency and ejaculation duration but not the number of pelvic thrusts during ejaculation were significantly correlated with the female's PER. In addition, pre-ejaculatory intromission frequency was significantly correlated with ejaculation duration. Partial correlation analysis suggested that pre-ejaculatory intromission frequency affected ejaculation duration which, in turn, influenced the female's PER. This finding was further supported by the evidence that ejaculation duration and the female's PER were significantly shorter in tests in which the male ejaculated on the first or second intromission. PMID:9523914
Yang, L Y; Clemens, L G
Timed-mated Sprague-Dawley rats (28 to 32\\/group) were exposed to boric acid (BA) in the diet from Gestational Day (GD) 0 to 20. Dietary concentrations of added BA (0%, 0.025%, 0.050%, 0.075%, O.lOO%, or 0.200%) yielded average daily intakes equivalent to 0,3, 6, 10, 13, or 25 mg boron\\/kg body weight\\/d. Dams and their fetuses were evaluated for evidence of maternal
Embryotoxicity and fetotoxicity following intraperitoneal administrations of hexavalent chromium to pregnant rats.
Heavy metals are omnipresent in the environment, and industrial use has greatly increased their presence in soil, water and air. Their inevitable transfer to the human food chain remains an important environmental issue as many heavy metals cause a range of toxic effects, including developmental toxicity. Administration of chromium VI (1 and 2 mg/kg as potassium dichromate) through intraperitoneal (i.p.) injection during organogenesis (days 6 to 15 of gestation) in rats revealed embryo- and fetotoxic effects. Reduced fetal weight, retarded fetal development, number of fetuses per mother and high incidences of dead fetuses and resorptions in treated mothers were also observed. Gross morphological abnormalities, such as displayed form of edema, facial defect, lack of tail, hypotrophy, severs subdermal haemorrhage patches and hypotrophy of placenta were observed in fetuses after chromium VI-treated mothers. A skeletal development of fetuses presented an incomplete ossification in nasal, cranium, abdominal or caudal bones in rats treated with 1 mg/kg of chromium, whereas rats treated with 2 mg/kg showed ossification and absence of the sacral vertebrae compared with the control. At a higher dose of chromium, histological changes were found in fetuses with atrophy of theirs vital organs. Placental histological observations revealed a pronounced morphological alteration, with atrophy of decidual cells, a degenerated of chorionic villi and hypertrophy of blood lacuna. The present study suggests a risk to the developing embryo when the mother is exposed to a high concentration of chromium VI during organogenesis. PMID:21205386
Marouani, Neila; Tebourbi, Olfa; Mokni, Moncef; Yacoubi, Mohamed Tahar; Sakly, Mohsen; Benkhalifa, Moncef; Ben Rhouma, Khémais
Effects of prenatal testosterone propionate on the sexual development of male and female rats: a dose-response study.
Testosterone plays a major role in male sexual development. Exposure of females to testosterone in utero can induce masculine characteristics such as anovulation, increased anogenital distance (AGD), absence of nipples, retention of male-like tissues, and agenesis of the lower vagina. In addition, high levels of androgens during fetal development can lead to toxic effects such as reduced litter size and viability. The study of the effects of testosterone administration during sexual differentiation provides a foundation for understanding the effects of environmental androgens on fetuses, a sensitive subpopulation. In the current study, we investigated the ability of a range of concentrations of testosterone propionate (TP) administered prenatally to masculinize female and alter male offspring, and measured maternal and fetal T levels. Pregnant Sprague-Dawley rats were dosed by sc injection on gestational day (GD) 14-19 (GD 1= day of plug) with either corn oil (vehicle; 0.1 ml/rat) or with 0.1 ml of TP solution at 0.1, 0.5, 1, 2, 5, or 10 mg/0.1 ml. Parturition was delayed at 2, 5, and 10 mg TP, litter size was reduced at 5 and 10 mg TP, and pup weight was significantly reduced in both sexes at 0.5 mg TP and higher doses. Viability of offspring was unaffected at any dosage level. Androgenic effects seen at 0.5 mg TP in females included increased AGD at weaning and adulthood, reduced number of areolas and nipples, cleft phallus, small vaginal orifice, and presence of prostate tissue. This dose of TP elevated maternal T levels 10x but had no effect on fetal T levels. At 1 mg TP and above, female AGD on postnatal day (PND) 2 (or postcoital day 24 [gestation length = 22(1/2)]) was increased; areolas and nipples were virtually eliminated; levator ani muscle, bulbourethral glands, and seminal vesicles (2 mg TP and above) were present; none of the females developed a vaginal orifice and many females in the 1 and 2 mg TP dose groups developed a greatly distended, fluid-filled uterus after puberty. Maternal T levels at 1 mg TP were elevated 30x, and female fetal T levels showed an 80% increase. Male offspring displayed a reduced AGD and body weight on PND 2 at 0.5 mg TP and higher doses. These effects were not evident by weaning and male offspring displayed no malformations. We conclude that gestational administration of 0.5 and 1 mg TP masculinizes female offspring without greatly affecting pup viability or pregnancy of the dam. This study provides a useful model for in utero testing of environmental androgens for their potential to induce developmental abnormalities. PMID:11752687
Wolf, Cynthia J; Hotchkiss, Andrew; Ostby, Joseph S; LeBlanc, Gerald A; Gray, L Earl
Stimulation of contraction of pregnant rat uterus in vitro by non-dechlorinated and microbially dechlorinated mixtures of polychlorinated biphenyls.
A previous study of six polychlorinated biphenyl (PCB) congeners showed that PCBs with four or fewer chlorines and ortho substitution stimulate uterine contraction frequency in vitro, whereas congeners with a greater number of chlorines or non-ortho substitution are inactive in vitro. We tested the hypothesis that PCB mixtures stimulate uterine contractions in a manner inversely related to the degree of chlorination and the presence of chlorines in the ortho- position of the biphenyl constituents of the mixtures. Uterine strips from pregnant rats were suspended in standard muscle baths and analyzed for changes in isometric contractions in response to in vitro exposure to commercial PCB mixtures (Aroclors) and their dechlorinated products after microbial degradation. The PCB mixtures Aroclor 1242, 1248, and 1254 significantly stimulated uterine contraction frequency, and the least chlorinated mixture, Aroclor 1242, was the most potent stimulant. Microbes from Hudson River sediment dechlorinated Aroclor 1242 and Aroclor 1254 under reducing conditions to produce mixtures with an increased proportion of ortho-substituted congeners with one or two chlorine substitutions. The PCB mixtures that had undergone microbial reductive dechlorination stimulated uterine contraction frequency to a significantly greater extent than the parent mixtures. These results show that increased uterotonic activity was associated with decreased chlorination and increased ortho substitution of the biphenyl constituents of the mixtures.
Bae, J; Mousa, M A; Quensen, J F; Boyd, S A; Loch-Caruso, R
Effect of restricted food supply to pregnant rats inhaling carbon monoxide on fetal weight, compared with cigarette smoke exposure
Although many studies have shown that cigarette smoking during gestation retarded the intrauterine fetal growth, resulting in the decreased birth weight in babies born to smoking mothers, neither causal substance nor mechanism of action to disturb fetal growth has been firmly established yet. Based on the human and animal studies, researchers have implied that fetal hypoxia induced by carbon monoxide (CO) in the cigarette smoke to be responsible for the event. A shortage in energy intake in smoking mothers also has been suspected to cause the retardation in fetal development. In the previous results (Tachi and Aoyama 1983), the weight increment in CO exposed animals was greater than that in the smoke exposed group. The phenomenon seemed to indicate that the reduction in the food intake occurs in animals which inhale the cigarette smoke, and induces the disturbance of fetal development in association with CO. In the present study, so as to evaluate the role of energy intake upon the fetal development in utero, the experiment of paired feeding with pregnant rats exposed to cigarette smoke is designed in animals which inhale the cigarette smoke, CO, or room air, following after the observation of the quantity of food taken by mothers exposed to cigarette smoke, CO, or room air.
Tachi, N.; Aoyama, M.
Effect of subchronic administration of methyl parathion on in vivo protein synthesis in pregnant rats and their conceptuses
Pregnant rats received daily po doses of the organophosphate methyl parathion (MPTH) from Day 6 through Day 15 or 19 of gestation at doses causing no (1.0 mg/kg) or minimal (1.5 mg/kg) signs of maternal toxicity. Following the dose of MPTH on Day 15 or 19, in vivo protein synthesis was measured 0.5, 1.0, and 2.0 hr after sc injection of L-(1-/sup 14/C)valine at a dose of 5 microCi/mmol/100 g body wt. The specific activity of (/sup 14/C)valine in the free amino acid pool and protein bound pool was significantly reduced in various regions of maternal brain and in maternal viscera, placenta, and whole embryos (Day 15), and in fetal brain and viscera (Day 19). The inhibitory effect of MPTH on net protein synthesis was dose dependent, greater on Day 19 than 15 of gestation and more pronounced in fetal than in maternal tissues.
Gupta, R.C.; Thornburg, J.E.; Stedman, D.B.; Welsch, F.
Statistical determination of whole-body average SARs in a 2 GHz whole-body exposure system for unrestrained pregnant and newborn rats
NASA Astrophysics Data System (ADS)
A 2 GHz whole-body exposure to rats over a multigeneration has been conducted as part of bio-effect research in Japan. In this study, the rats moved freely in the cage inside the exposure system. From observation of the activity of rats in the cage, we found that the rats do not stay in each position with uniform possibility. In order to determine the specific absorption rate (SAR) during the entire exposure period with high accuracy, we present a new approach to statistically determine the SAR level in an exposure system. First, we divided the rat cage in the exposure system into several small areas, and derived the fraction of time the rats spent in each small area based on the classification of the documentary photos of rat activity. Then, using the fraction of time spent in each small area as a weighting factor, we calculated the statistical characteristics of the whole-body average SAR for pregnant rats and young rats during the entire exposure period. As a result, this approach gave the statistical distribution as well as the corresponding mean value, median value and mode value for the whole-body SAR so that we can reasonably clarify the relationship between the exposure level and possible biological effect.
Wang, Jianqing; Wake, Kanako; Kawai, Hiroki; Watanabe, Soichi; Fujiwara, Osamu
Sexual behavior of female rats in a multiple-partner preference test.
In this study, sexually experienced female rats were tested in a multiple-partner preference test (MPPT) in which they were allowed to pace their sexual contacts with four sexually active males. Four cylinders, with a small hole through which only the female could move freely from one cylinder to another, were assembled forming in the center an empty compartment. An intact female was placed in the central compartment and a sexually active male in each cylinder. Female sexual behavior was analyzed throughout the estrus cycle in four consecutive days. Each daily test lasted 15 min. The percentage of exits after intromission or ejaculation was significantly higher than the percentage of exits after each mount. The female spent significantly longer time with one of the males. We designated this male as the preferred male (PM). Although in each of the 4 days studied, females spent significantly longer time with the PM, however, the male selected was not the same throughout the estrus cycle. The number of entries into the compartment of the PM was significantly higher and increased around proestrus. Compared to previous studies, pacing behavior was notably lower in the conditions of the MPPT. No significant differences were observed during the estrous cycle concerning the other parameters recorded. The present results suggest that the MPPT could be a good model to study partner preference in the female rat. PMID:15708757
Ferreira-Nuńo, A; Morales-Otal, A; Paredes, Raúl G; Velázquez-Moctezuma, J
The Ontogeny of Exploratory Behavior in Male and Female Adolescent Rats (Rattus norvegicus)
During adolescence, rats gain independence from their mothers and disperse from the natal burrow, with males typically dispersing further than females. We predicted that, if dispersal patterns are associated with responsiveness to novelty, exploratory behavior in novel environments would increase across adolescence, and males would explore more than females. Alternatively, females might explore more than males, if females are more motivated than males to learn about the immediate environment or if females have poorer spatial abilities than males. Twenty-five male and 21 female rats were exposed to two novel environments (open field and elevated plus-maze) during early, mid-, or late adolescence. Total locomotion and amount of exploration directed towards aversive areas increased across adolescence, even when body weight was included as a covariate. Female adolescents locomoted more and spent more time exploring aversive areas than males. Developmental changes in neural function potentially underlie age and sex differences in exploratory behavior. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 513–520, 2009.
Lynn, Debra A; Brown, Gillian R
Production of fat-1 transgenic rats using a post-natal female germline stem cell line.
Germline stem cell lines possess the abilities of self-renewal and differentiation, and have been established from both mouse and human ovaries. Here, we established a new female germline stem cell (FGSC) line from post-natal rats by immunomagnetic sorting for Fragilis, which showed a normal karyotype, high telomerase activity, and a consistent gene expression pattern of primordial germ cells after 1 year of culture. Using an in vitro differentiation system, the FGSC line could differentiate into oocytes. After liposome-based transfection with green fluorescent protein (GFP) or fat-1 vectors, the FGSCs were transplanted into the ovaries of infertile rats. The transplanted FGSCs underwent oogenesis, and the rats produced offspring carrying the GFP or fat-1 transgene after mating with wild-type male rats. The efficiency of gene transfer was 27.86-28.00%, and 2 months was needed to produce transgenic rats. These findings have implications in biomedical research and potential applications in biotechnology. PMID:24258451
Zhou, Li; Wang, Lei; Kang, Jing X; Xie, Wenhai; Li, Xiaoyong; Wu, Changqing; Xu, Bo; Wu, Ji
Chronic effects of atrazine on estrus and mammary tumor formation in female Sprague?Dawley and Fischer 344 rats
The chronic effects of dietary administration of atrazine at levels as high as 400 ppm on selected endocrine and tumor profiles were evaluated in Fischer 344 and Sprague?Dawley female rats. The study showed that lifetime dietary administration of atrazine at a maximum tolerated dose (MTD) to Sprague?Dawley female rats caused (1) lengthening of the estrous cycle, (2) increased number of
Lawrence T. Wetzel; Louis G. Luempert III; Charles B. Breckenridge; Merrill O. Tisdel; James T. Stevens; Ajit K. Thakur; Pamela J. Extrom; J. Charles Eldridge
Inhibitory Effect of Baclofen on Lordosis in Female and Male Rats with Dorsal Raphe Nucleus Lesion or Septal Cut
The inhibitory effect of baclofen, a GABA? receptor agonist, on lordosis was examined in female and male rats with dorsal raphe nucleus lesions (DRL) or cut of the septal fibers (ARD). Both female and male DRL and ARD rats showed higher lordosis quotients (LQ) than corresponding controls without brain surgery. This indicates that the dorsal raphe nucleus and the septum
Masaki Kakeyama; Korehito Yamanouchi
Effects of Estrogen Treatment on the Size of Receptive Field and Response Threshold of Pudendal Nerve in the Female Rat
Receptive fields and response thresholds were determined by stimulation with a camel hair brush and von Frey hairs during recording from a specific branch of the pudendal nerve, in untreated and estrogen-treated ovariectomized female rats. The receptive field of this pudendal nerve branch is located on the perineal skin of the female rat, extending in some cases onto the back
L.-M. Kow; D. W. Pfaff
Effects of crude root extract of Polygonum hydropiper on estrous cycle and induction of reversible sterility in female albino rat
Summary Polygonum hydropiper is a wild plant found in Assam, a North-Eastern province of India. Tradition prevails among the folk women of Assam to use the root of this herb for fertility control. In the present investigation crude methanolic extract of root of this plant was tested for anti-fertility property in female albino rat. Adult cycling female rats were administered
Hazarika A; Sarma HN
Combined and individual administration of diethyl phthalate and polychlorinated biphenyls and its toxicity in female Wistar rats
Polychlorinated biphenyls (PCBs) are persistent environmental pollutants and known to act as xenoestrogens. PCBs and diethyl phthalate (DEP) are ubiquitous environmental pollutants because both are used as plasticizers and in various other industrial applications. Therefore, a study was undertaken to evaluate the interactive toxicity of DEP and PCBs in young female Wistar rats. Healthy young female albino rats of Wistar
Contzen Pereira; C. Vaman Rao
The Time of Prenatal Androgen Exposure Affects Development of Polycystic Ovary Syndrome-Like Phenotype in Adulthood in Female Rats
Background: Polycystic ovary syndrome (PCOS) is one of the most common reproductive disorders in women. Previous studies have shown that prenatal exposure of female fetuses to androgen can be considered an important factor in the development of PCOS. Objectives: In the present study we aimed to examine the effects of prenatal exposure of female rat fetuses to previously documented doses of testosterone on different embryonic days on the development of PCOS phenotype in adulthood. Materials and Methods: Pregnant rats were divided into four groups, experimental and control groups. Three mg of free testosterone was administered subcutaneously to experimental group 1 on gestational days 16-19, daily and 20 mg on day 20, to experimental group 2, and the controls received solvent at the same times. Female offspring of these mothers aged between 90-100 days were examined for development and function of the reproductive system. Independent-sample student t test was used to compare the results between the experimental groups and controls. Results: Anogenital distance (P < 0.001) and clitoris length were significantly increased in the offspring of both experimental groups (P < 0.001 and P < 0.05 respectively). Nipples were not formed in the offspring of experimental group 1, whereas in experimental group 2 the number of nipples was unchanged. Vaginal length was significantly decreased in the offspring of experimental group 1 (P < 0.001), whereas in experimental group 2, no significant difference was observed. In the offspring of experimental group 1, hormonal profiles did not differ, but in experimental group 2, levels of testosterone (P < 0.05) and LH (P < 0.01) were significantly increased, but estrogen (P < 0.05) and anti-Mullerian hormone levels (P < 0.001) were significantly decreased. A significant increase in the number of preantral and antral follicles was observed in the ovaries of offspring of experimental group 1 (P < 0.05); whereas there was no such a difference in experimental group 2. Conclusions: The time of prenatal exposure to androgens may have a significant role in the development of PCOS. Increased prenatal androgen levels are associated with hormonal changes and morphological disorders of the reproductive system. Therefore, avoiding exposure to androgen excess during critical periods of fetal development may prevent or reduce adulthood PCOS manifestations caused by prenatal excess androgen.
Ramezani Tehrani, Fahimeh; Noroozzadeh, Mahsa; Zahediasl, Saleh; Piryaei, Abbas; Hashemi, Somayeh; Azizi, Fereidoun
Peripubertal Administration of Icariin and Icaritin Advances Pubertal Development in Female Rats
Epimedii Herba is a traditional medicinal herb used in Korea and China and exerts estrogenic activity. In this study, we investigated the effect of peripubertal administration of Epimedii Herba on pubertal development in female rats using a modified protocol of the rodent 20-day pubertal female assay. Female Sprague-Dawley rats (21 days old after weaning, 10 rats per group) were divided into five groups: saline (Con), ethinyl estradiol (E2), Epimedii Herba ext (Ext), icariin (ICI), and icaritin (ICT), which were administered by oral gavage (E2 by subcutaneous injection) from postnatal day (PND) 21 through PND40. The time to vaginal opening (VO) was shorter for the Epimedii groups, particularly for the ICT group (p<0.05). Treatment with ICI and ICT significantly increased the duration of the estrus cycle (ICI, 2.78 days; ICT, 4.0 days; control, 1.78 days). Ovary weight was reduced by E2 treatment and increased by the Ext, ICI, and ICT treatments while the weight of the uterus and pituitary glands increased significantly only in the E2 and ICT groups. Although Epimedii Herba displayed relatively weak estrogenic activity, its repeated administration could affect pubertal development in female rats.
Kang, Hyun Ku; Lee, Sang-Bum; Kwon, Hyosuk; Sung, Chung Ki; Park, Young In; Dong, Mi-Sook
Effects of Cadmium, Calcium, Age and Parity on Bone Mineral, Density and Strength in Female Rats.
National Technical Information Service (NTIS)
Weanling female rats were fed diets containing one of three levels of calcium and one of four levels of cadmium in the drinking water. Approximately 10 animals from each group were sacrificed after the first pregnancy and the remaining animals after the f...
B. F. Hammond
The present study was designed to evaluate the influence of acrylamide (ACR) on male and female reproductive function. Male rats received ACR in drinking water (50, 100, or 200 ppm) for up to 10 wk. Copulatory behavior, semen, and (for controls and 100 ppm only) fertility and fet...
Isolation and characterization of an alicyclic amine N-sulfotransferase from female rat liver.
An alicyclic amine N-sulfotransferase sulfonating 4-phenyl-1,2,3,6-tetrahydropyridine (PTHP) was purified from female rat liver cytosol and showed a homogenous band with a molecular weight of 30500 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme, designated NST-1, catalyzed sulfonation not only of the alicyclic amine but also dehydroepiandrosterone, a typical substrate of hydroxysteroid sulfotransferase (STs), but had little sulfonating activity towards 2-naphthol, a typical substrate of aryl STs. The N-terminal amino acid sequence for the first 24 residues had a high homology with those of rat liver hydroxysteroid STs. Therefore, it is suggested that NST-1 is classified as a member of the hydroxysteroid ST. Immunoblot analysis of male and female rat liver cytosol, carried out by using rabbit antisera raised against NST-1, indicated that the female cytosol contained a higher level of the enzyme than that of male. The marked sex difference in the expression level of NST-1 was in good accordance with the previous demonstration that female rat liver cytosol catalyzed sulfonation of PTHP to a greater extent than that of male. PMID:7820098
Naritomi, Y; Niwa, T; Shiraga, T; Iwasaki, K; Noda, K
Acute Oral Toxicity of DMSO (Dimethyl Sulfoxide) Process Stream Samples in Male and Female Rats.
National Technical Information Service (NTIS)
The acute toxicities of a single oral dose of the DMSO process stream samples, DMSO Evaporator Sludge, DMSO Recycle Solvent, and Virgin DMSO, were determined in male and female albino Sprague-Dawley rats. The DMSO Evaporator Sludge and Virgin DMSO solutio...
C. W. White J. Rodriguez G. E. Marrs
Hypothermia and delayed fever in the male and female rat exposed to chlorpyrifos
Chlorpyrifos (CHL) is a commonly used organophosphate (OP) pesticide which irreversibly inhibits acetylcholinesterase activity in the CNS. Little is known regarding the thermoregulatory effects of CHL when administered orally and whether the sensitivity to CHL is affected by sex. To address these issues, male and female rats of the Long-Evans strain were administered 0, 10, 50, or 80 mg\\/kg CHL
Christopher J. Gordon; Tholeathcus A. Grantham; Ying Yang
17ß-Estradiol Is Necessary for Extinction of Cocaine Seeking in Female Rats
ERIC Educational Resources Information Center
Human and preclinical models of addiction demonstrate that gonadal hormones modulate acquisition of drug seeking. Little is known, however, about the effects of these hormones on extinction of drug-seeking behavior. Here, we investigated how 17ß-estradiol (E[subscript 2]) affects expression and extinction of cocaine seeking in female rats. Using a…
Twining, Robert C.; Tuscher, Jennifer J.; Doncheck, Elizabeth M.; Frick, Karyn M.; Mueller, Devin
The Endocrine Profile of Intact Female Rats on the Day of Proestrus Following Exposure to Atrazine. RL Cooper, A Buckalew, SC Laws and TE Stoker Endocrinology Branch, RTD, NHEERL, ORD, U.S. EPA, RTP, NC, 27711. The chlorotriazine herbicide, atrazine, has been sho...
Effects of altered food intake during pubertal development in male and female Wistar rats
The U.S.EPA is currently validating assays that will be used in a Tier I Screening Battery to detect endocrine disrupting chemicals. A primary concern with the Protocols for the Assessment of Pubertal Development and Thyroid Function in Juvenile Male and Female Rats is that a non...
Cerebral microgyria, thalamic cell size and auditory temporal processing in male and female rats
Induction of microgyria by freezing injury to the developing somatosensory cortex of neonatal rats causes a defect in fast auditory processing in males, but not in females. It was speculated that early damage to the cortex has sexually dimorphic cascading effects on other brain regions mediating auditory processing, which can lead to the observed behavioral deficits. In the current series
Amy E. Herman; Albert M. Galaburda; R. Holly Fitch; Alex R. Carter; Glenn D. Rosen
Triadimefon is a widely used systemic fungicide, yet there is little published information on its effects in mammals. This study describes the effects of triadimefon in male and female rats using a functional observational battery (FOB), motor activity (measured in a figure-eight...
Effects of Altered Food Intake during Pubertal Development in Male and Female Wistar Rats
The U.S. Environmental Protection Agency is currently validating assays that will be used in a Tier I Screening Battery to detect endocrine disrupting chemicals. A primary concern with the Protocols for the Assessment of Pubertal Development and Thyroid Function in Juvenile Male and Female Rats is that a nonspecific reduction in body weight (BWT) during the expo- sure period may
Susan C. Laws; Tammy E. Stoker; Janet M. Ferrell; Michelle G. Hotchkiss; Ralph L. Cooper
Coping strategies in male and female rats exposed to multiple stressors
Because of the pathogenic effects of chronic stress exposure, it is important to identify factors, such as effective coping strategies, that mitigate stress-induced pathology. Of interest in the present study was the consistency of behavioral responses across a diverse array of stressors. Sixteen male and 16 female Long–Evans rats were assigned to either a stress or control group. The stressed
Thomas Campbell; Stacie Lin; Courtney DeVries; Kelly Lambert
Environmental enrichment promotes robust functional and histological benefits in female rats after controlled cortical impact injury.
Environmental enrichment (EE) consistently induces marked benefits in male rats after traumatic brain injury (TBI), but whether similar efficacy extends to females is not well established. Hence, the aim of this study was to reassess the effect of EE on functional and histological outcome in female rats after brain trauma. Twenty-four normal cycling adult female rats underwent verification of estrous stage prior to controlled cortical impact (CCI) or sham injury and then were assigned to EE or standard (STD) housing. Motor function was assessed with beam-balance/beam-walk and rotarod tasks on post-operative days 1-5 and every other day from 1-19, respectively. Spatial learning/memory was evaluated in a Morris water maze on days 14-19. Morphologically intact hippocampal CA(1/3) cells and cortical lesion volume were quantified 3 weeks after injury. No differences were observed between the EE and STD sham groups in any endpoint measure and thus the data were pooled. In the TBI groups, EE improved beam-balance, beam-walk, rotarod, and spatial learning performance vs. STD (p's<0.05). EE also provided significant histological protection as confirmed by increased CA(1/3) cell survival and decreased cortical lesion size vs. STD. These data demonstrate that EE confers robust benefits in female rats after CCI injury, which parallels numerous studies in males and lends further credence for EE as a preclinical model of neurorehabilitation. PMID:23333563
Monaco, Christina M; Mattiola, Vincent V; Folweiler, Kaitlin A; Tay, Justin K; Yelleswarapu, Narayana K; Curatolo, Lauren M; Matter, Ashley M; Cheng, Jeffrey P; Kline, Anthony E
The extrinsic innervation of the pelvic organs in the female rat
The extrinsic innervation of the pelvic organs in neonatal and adult female rats is described. Mainly an in toto acetylcholinesterase method is used; moreover, acetyl-cholinesterase is demonstrated in sections. The hypogastric plexus is defined as the nerve plexuses caudal to the inferior mesenteric ganglia comprising the uterine cervical ganglia and various smaller ganglia. The origin of the hypogastric plexus is
B. Baljet; J. Drukker
MASCULINIZATION OF FEMALE RATS BY PRENATAL TESTOSTERONE PROPIONATE IS PARTIALLY ATTENUATED BY VINCLOZOLIN Cynthia Wolf1,2, Gerald LeBlanc2, Andrew Hotchkiss3, Jonathan Furr1, L Earl Gray, Jr.1 1USEPA, Reproductive Toxicology Division, RTP, NC 27711, 2Dept. Molecular and En...
Effects of Formalin Pain on Hippocampal c- Fos Expression in Male and Female Rats
Immediate early genes are crucial intermediates in a cascade linking membrane stimulation to long-term alterations of neuronal activity. In the present experiment, we performed immunohistochemistry for c-Fos to determine the effects of persistent pain on cells of the hippocampus of male and female rats. Animals were subcutaneously injected with formalin (50 ?l, 10%) and perfused: 2 h later, time 2;
Ilaria Ceccarelli; Andrea Scaramuzzino; Anna Maria Aloisi
Female Sprague-Dawley CD rats were fed 0, 60, 80, 100, 120 and 140 ppm hexachlorobenzene (HCB) continuously in the diet and 2 successive litters raised. These doses were selected to range from approximately the no observable effect level to lethality in suckling offspring of trea...
Effects of anti-estrogens on bone in castrated and intact female rats
Summary The effects of the antiestrogens tamoxifen and keoxifene on the bone density of intact and ovariectomized female rats were determined after 4 months of therapy. The antiestrogens did not cause a decrease in bone density in intact animals, although uterine wet weight did decrease. Ovariectomy caused an increase in body weight (25%) and a significant decrease in femur density
V. Craig Jordan; Erik Phelps; J. Urban Lindgren
Sex hormone-induced mammary carcinogenesis in female Noble rats: the role of androgens
Breast cancer is the most common cancer and the second most frequent cause of cancer death in women. Despite extensive research, the precise mechanisms of breast carci- nogenesis remain unclear. We have shown that in female rats, treatment with a combination of oestrogen and testo- sterone can induce a high incidence of mammary cancer. The dosage of testosterone affects only
B. Xie; S. W. Tsao; Y. C. Wong
Female rats were exposed to the formamidine pesticide chlordimeform (50 mg/kg) or sodium pentobarbital (35 mg/kg) at selected times during the estrous cycle and the effect of this treatment on pregnancy outcome was evaluated. When exposed on the afternoon of vaginal proestrus, bo...
Hippocampal dendritic spine and synapse numbers in female rats vary across the estrous cycle and following experimental manipulation of hormone levels in adulthood. Based on behavioral studies demonstrating that learning patterns are altered following puberty, we hypothesized that dendritic spine number in rat hippocampal CA1 region would change post-pubertally. Female Sprague-Dawley rats were divided into prepubertal (postnatal day (P) 22), peripubertal (P35) and post-pubertal (P49) groups, with the progression of puberty evaluated by vaginal opening, and estrous cyclicity subsequently assessed by daily vaginal smears. Spinophilin immunoreactivity in dendritic spines was used as an index of spinogenesis in area CA1 stratum radiatum (CA1sr) of hippocampus. First, electron microscopy analyses confirmed the presence of spinophilin specifically in dendritic spines of CA1sr, supporting spinophilin as a reliable marker of hippocampal spines in young female rats. Second, stereologic analysis was performed to assess the total number of spinophilin-immunoreactive puncta (i.e. spines) and CA1sr volume in developing rats. Our results indicated that the number of spinophilin-immunoreactive spines in CA1sr was decreased 46% in the post-pubertal group compared to the two younger groups, whereas the volume of the hippocampus underwent an overall increase during this same developmental time frame. Third, to determine a potential role of estradiol in this process, an additional group of rats was ovariectomized (OVX) prepubertally at P22, then treated with estradiol or vehicle at P35, and spinophilin quantified as above in rats perfused on P49. No difference in spinophilin puncta number was found in OVX rats between the two hormone groups, suggesting that this developmental decrease is independent of peripheral estradiol. These changes in spine density coincident with puberty may be related to altered hippocampal plasticity and synaptic consolidation at this phase of maturity.
Yildirim, Murat; Mapp, Oni M.; Janssen, William G.M.; Yin, Weiling; Morrison, John H.; Gore, Andrea C.
Expression and biological activity of parathyroid hormone-related peptide in pregnant rat uterine artery: any role for 8-iso-prostaglandin F2alpha?
PTHrP is produced in vessels and acts as a local modulator of tone. We recently reported that PTHrP(1-34) is able to induce vasorelaxation in rat uterine arteries, but in pregnancy, this response is blunted and becomes strictly endothelium dependent. The present study aimed to get insights into the mechanisms involved in these changes because the adaptation of uterine blood flow is essential for fetal development. On d 20 of gestation, RT-PCR analysis of uterine arteries showed that PTH/PTHrP receptor (PTH1R) mRNA expression was decreased, whereas that of PTHrP mRNA was increased. This was associated with a redistribution of the PTHrP/PTH1R system, with both PTH1R protein and PTHrP peptide becoming concentrated in the intimal layer of arteries from pregnant rats. On the other hand, the blunted vasorelaxation induced by PTHrP(1-34) in uterine arteries from pregnant rats was specifically restored by indomethacin and a specific cyclooxygenase-2 inhibitor, NS 398. This was associated with an increase in cyclooxygenase-2 expression and in 8-iso-prostaglandin F(2alpha) release when uterine arteries from pregnant rats were exposed to high levels of PTHrP(1-34). Most interestingly, 8-iso-prostaglandin F(2alpha) itself was able to increase PTHrP expression and reduce PTH1R expression in cultured rat aortic smooth muscle cells. These results suggest a local regulation of uterine artery functions by PTHrP during pregnancy resulting from PTH1R redistribution. Moreover, they shed light on a potential role of 8-iso-prostaglandin F(2alpha). PMID:18048500
Meziani, Ferhat; Tesse, Angela; Welsch, Sandra; Kremer, Hélčne; Barthelmebs, Mariette; Andriantsitohaina, Ramaroson; Schneider, Francis; Gairard, Alexis
Early life stress impairs fear conditioning in adult male and female rats.
We demonstrated that neonatal isolation (1-h pup isolation; postnatal days 2-9) impairs context-induced fear conditioning in adult male rats and tends to enhance this effect and foot shock sensitivity in females. In this study, we examine the effects of brief (i.e., handling; 15 min) and prolonged (3 h) maternal separations (postnatal days 1-21) on fear conditioning and foot shock sensitivity in adult male and female rats. Identical training and test conditions from our prior study were employed so comparisons of the three early life stressors could be made. Context- and cue-elicited freezing and ultrasonic vocalizations (USVs; 22 kHz) were measured after 10 tone-shock training trials in Experiment 1. In Experiment 2, foot shock responses (flinch, jump, sonic vocalizations) to escalating shock levels were assessed. Brief maternal separation impaired context- and cue-conditioned fear in rats of both sexes as assessed by USVs. Prolonged maternal separation only impaired context fear in female rats. There were no effects on foot shock sensitivity. Results of this and other studies suggest that early life stress impairs fear conditioning in adult rats whereas stress experienced in adulthood has the opposite effect. These opposing effects may reflect developmental differences on stress-induced alterations on hippocampal regulation of the hypothalamic-pituitary-adrenal axis. PMID:16626646
Kosten, Therese A; Lee, Hongjoo J; Kim, Jeansok J
Influences of chemical sympathectomy and simulated weightlessness on male and female rats
NASA Technical Reports Server (NTRS)
Consideration is given to a study aimed at determining whether the sympathetic nervous system is associated with the changes in maximum oxygen consumption (VO2max), run time, and mechanical efficiency observed during simulated weightlessness in male and female rats. Female and male rats were compared for food consumption, body mass, and body composition in conditions of simulated weightlessness to provide an insight into how these parameters may influence aerobic capacity and exercise performance. It is concluded that chemical sympathectomy and/or a weight-bearing stimulus will attenuate the loss in VO2max associated with simulated weightlessness in rats despite similar changes in body mass and composition. It is noted that the mechanisms remain unclear at this time.
Woodman, Christopher R.; Stump, Craig S.; Stump, Jane A.; Sebastian, Lisa A.; Rahman, Z.; Tipton, Charles M.
Effects of Estrogen and Progesterone on the Escalation of Cocaine Self-Administration in Female Rats During Extended Access
Estrogen increases and progesterone decreases the acquisition and reinstatement of cocaine-seeking behavior in female rats. Here estrogen and progesterone were studied for their effects on the escalation of cocaine self-administration in female rats. The rats received ovariectomy (OVX) or sham (SH) surgery and were treated with estradiol benzoate (0.05 mg\\/kg sc) and\\/or progesterone (0.5 mg\\/kg) or vehicle (indicated by E,
Erin B. Larson; Justin J. Anker; Luke A. Gliddon; Kyah S. Fons; Marilyn E. Carroll
Effects of Chronic Restraint Stress and 17-?-Estradiol Replacement on Oxidative Stress in the Spinal Cord of Ovariectomized Female Rats
Previous studies have shown sex-specific oxidative changes in spinal cord of rats submitted to chronic stress, which may be\\u000a due to gonadal hormones. Here, we assessed total radical-trapping potential (TRAP), superoxide dismutase (SOD) and glutathione\\u000a peroxidase (GPx) activities and lipid peroxidation (evaluated by the TBARS test) in the spinal cord of ovariectomized (OVX)\\u000a female rats. Female rats were subjected to
Leonardo M. Crema; Luisa A. Diehl; Ana P. Aguiar; Lúcia Almeida; Fernanda U. Fontella; Letícia Pettenuzzo; Deusa Vendite; Carla Dalmaz
Effect of valproic acid on /sup 65/Zn distribution in the pregnant rat
The effect of valproic acid on the distribution of gavaged /sup 65/Zn in maternal and embryonic tissue of Sprague-Dawley rats was examined 24 h after gavaging of the drug on d 13 of pregnancy. Valproic acid treatment resulted in a significantly higher retention of /sup 65/Zn in maternal liver and lower amounts in uterus, placenta and embryos than in controls. Compared to controls, gel chromatography of maternal liver from valproic acid-treated dams showed higher /sup 65/Zn counts associated with a protein peak of molecular weight of 6,500, the approximate molecular weight of the Zn-binding protein metallothionein. These results support the idea that the teratogenicity of valproic acid is in part due to an induction of embryonic Zn deficiency secondary to a drug-induced sequestering of Zn into maternal liver that results in a decrease in maternal plasma Zn and subsequent reduction in embryonic Zn uptake.
Keen, C.L.; Peters, J.M.; Hurley, L.S.
Effects of Hypergravity Exposure On Plasma Oxytocin Concentrations In Pregnant and Lactating Rat Dams
NASA Technical Reports Server (NTRS)
Rat dams and offspring were exposed to 1.5-g, 1.75-g or 2.0-g hypergravity (hg) from Gestational day (G) 11 until Postnatal day (P) 10. To ascertain the role of maternal factors in reduced postnatal body weights of offspring developed in hg, the dams' lactational hormones were measured. Oxytocin (OT), the major hormone responsible for milk ejection, was reduced in hg dams whereas prolactin (Prl), involved in milk production, was unchanged. Video analyses of nursing behavior revealed that hg dams spent more time nursing relative to 1-g controls. We hypothesized impaired milk transfer from dam to pup, however pup body weight gains following a discrete suckling episode were comparable across conditions. Changes in lactational hormones and nursing behavior by dams exposed to hg do not account for reduced body masses of their offspring.
Baer, Lisa A.; Wade, Charles E.; Ronca, April E.; Dalton, Bonnie (Technical Monitor)
Effect of dietary copper deficiency on iron metabolism in the pregnant rat.
Cu and Fe metabolism are known to be linked, but the interactions during pregnancy are less well studied. In the present study we used rats to examine the effect of Cu deficiency during pregnancy on Fe and Cu levels in maternal and fetal tissue and on the gene expression profile of proteins involved in Cu and Fe metabolism in the placenta. Rats were fed diets with different Cu contents before and during pregnancy. Samples were collected on day 21 of gestation. Cu levels, ceruloplasmin activity and serum Fe all decreased in maternal serum of Cu-deficient animals. Maternal liver Fe inversely correlated with liver Cu. Placental Cu levels decreased with no change in Fe. Fe and Cu levels both decreased in the fetal liver. The drop in maternal liver Cu was significantly correlated with a decrease in organ weight of fetal liver, lung and kidney. No changes were observed in mRNA expression of Cu transporter 1, Menkes P-type Cu-ATPase 7A, Wilson P-type Cu-ATPase 7B, cytochrome-c oxidase, and Cu chaperone Atox1 in the placenta of Cu-deficient dams. Transferrin receptor 1 and the Fe-responsive element (IRE)-regulated divalent metal transporter 1 (DMT1) were up regulated; while ferroportin and non-IRE1-regulated DMT1 levels did not change. These data show that Cu deficiency during pregnancy not only has a direct effect on Fe levels but also regulates the expression of Fe transporters. The pattern closely mirrors that seen in Fe deficiency, suggesting that the changes are a consequence of the decrease in serum Fe, implying that the developing fetus not only suffers from Cu, but also from Fe deficiency. PMID:17298691
Andersen, Henriette S; Gambling, Lorraine; Holtrop, Grietje; McArdle, Harry J
Adolescent peer-rejection persistently alters pain perception and CB1 receptor expression in female rats.
Peer-interactions are particularly important during adolescence and teenagers display enhanced sensitivity toward rejection by peers. Social rejection has been shown to induce alterations in pain perception in humans. However, the neurobiological consequences of adolescent social rejection have yet to be extensively characterized, and no appropriate animal model is available. Here, we propose inadequate playful interactions in adolescent rats as a novel animal model for social peer-rejection and examine potential long-term consequences into adulthood. Acute social pairing of female adolescent Wistar rats with an age-matched rat from the less playful Fischer344 strain was found to alter social play and decrease pain reactivity, indicating Fischer rats as inadequate social partners for Wistar animals. Therefore, in a second experiment, adolescent female Wistar rats were either reared with another Wistar rat (adequate social rearing; control) or with a Fischer rat (inadequate social rearing; play-deprived). Beginning on day 50, all Wistar rats were group housed with same-strain partners and tested for behavioral, neurobiological and endocrine differences in adulthood. Playful peer-interactions were decreased during adolescence in play-deprived animals, without affecting social contact behavior. Consequently, adult play-deprived rats showed decreased pain sensitivity and increased startle reactivity compared to controls, but did not differ in activity, anxiety-related behavior or social interaction. Both groups also differed in their endocrine stress-response, and expression levels of the cannabinoid CB1 receptor were increased in the thalamus, whereas FAAH levels were decreased in the amygdala. The present animal model therefore represents a novel approach to assess the long-term consequences of peer-rejection during adolescence. PMID:23669059
Schneider, Peggy; Hannusch, Christin; Schmahl, Christian; Bohus, Martin; Spanagel, Rainer; Schneider, Miriam
In utero phthalate effects in the female rat: A model for MRKH syndrome?
Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome is characterized by uterine and vaginal canal aplasia in normal karyotype human females and is a syndrome with poorly defined etiology. Reproductive toxicity of phthalate esters (PEs) occurs in rat offspring exposed in utero, a phenomenon that is better studied in male offspring than females. The current study reports female reproductive tract malformations in the Sprague–Dawley rat similar to those characteristic of MRKH syndrome, following in utero exposure to a mixture of 5 PEs. We determined that females are ~2-fold less sensitive to the effects of the 5-PE mixture than males for reproductive tract malformations. We were not fully successful in defining the critical exposure period for females; however, incidence of malformations was 88% following dosing from GD8 to 19 versus 22% and 0% for GD8–13 and GD14–19, respectively. Overall, this study provides valuable information regarding female vulnerability to in utero phthalate exposure and further characterizes a potential model for the human MRKH syndrome.
Hannas, Bethany R.; Howdeshell, Kembra L.; Furr, Johnathan; Gray, L. Earl
In utero phthalate effects in the female rat: a model for MRKH syndrome.
Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by uterine and vaginal canal aplasia in normal karyotype human females and is a syndrome with poorly defined etiology. Reproductive toxicity of phthalate esters (PEs) occurs in rat offspring exposed in utero, a phenomenon that is better studied in male offspring than females. The current study reports female reproductive tract malformations in the Sprague-Dawley rat similar to those characteristic of MRKH syndrome, following in utero exposure to a mixture of 5 PEs. We determined that females are ?2-fold less sensitive to the effects of the 5-PE mixture than males for reproductive tract malformations. We were not fully successful in defining the critical exposure period for females; however, incidence of malformations was 88% following dosing from GD8 to 19 versus 22% and 0% for GD8-13 and GD14-19, respectively. Overall, this study provides valuable information regarding female vulnerability to in utero phthalate exposure and further characterizes a potential model for the human MRKH syndrome. PMID:23542816
Hannas, Bethany R; Howdeshell, Kembra L; Furr, Johnathan; Gray, L Earl
Presence of a Neural Mechanism for the Expression of Female Sexual Behaviors in the Male Rat Brain
Facilitatory and inhibitory neural mechanisms involved in the expression of female sexual behaviors in male rats were examined with a dual operation technique. Male rats were castrated and the preoptic area was dorsally deafferented (anterior roof deafferentation, ARD) in order to remove the forebrain lordosis-inhibitory system. Male rats with ARD displayed not only lordosis but also soliciting behaviors in response
Korehito Yamanouchi; Yasumasa Arai
Effect of dietary carbohydrates on glucagon and insulin receptors in genetically obese female Zucker rats.
Obese Zucker rats are hyperlipemic and mildly hyperglycemic. Because insulin and glucagon are involved in lipid and carbohydrate metabolism and they act via their receptors, we investigated the role of insulin and glucagon receptors in obese and lean female Zucker rats. Because dietary sucrose is more lipogenic than starch, we also studied the effect of dietary carbohydrates on the receptors. Significant phenotypic effect (obese greater than lean) was observed on plasma levels of glucose, triglyceride and insulin. Binding of insulin and glucagon to liver plasma membranes was significantly lower in obese rats than in lean rats. Lower insulin binding was due to a lower number of receptors as well as a lower affinity, whereas the lower glucagon binding was due only to a lower receptor number. Insulin binding in lean rats but not in obese rats was lower in sucrose-fed than in starch-fed rats. Diet had no effect on glucagon binding. We propose that in obese Zucker rats, in addition to hyperinsulinemia, impaired glucagon activity as manifested by decreased glucagon binding to target tissues may be an important contributor to the hyperlipemia and obesity. PMID:3039087
Bhathena, S J; Aparicio, P; Revett, K; Voyles, N; Recant, L
Maternal Programming of Sexual Behavior and Hypothalamic-Pituitary-Gonadal Function in the Female Rat
Variations in parental care predict the age of puberty, sexual activity in adolescence and the age at first pregnancy in humans. These findings parallel descriptions of maternal effects on phenotypic variation in reproductive function in other species. Despite the prevalence of such reports, little is known about potential biological mechanisms and this especially true for effects on female reproductive development. We examined the hypothesis that parental care might alter hypothalamic-pituitary-ovarian function and thus reproductive function in the female offspring of rat mothers that vary pup licking/grooming (LG) over the first week postpartum. As adults, the female offspring of Low LG mothers showed 1) increased sexual receptivity; 2) increased plasma levels of luteinizing hormone (LH) and progesterone at proestrus; 3) an increased positive-feedback effect of estradiol on both plasma LH levels and gonadotropin releasing-hormone (GnRH) expression in the medial preoptic region; and 4) increased estrogen receptor ? (ER?) expression in the anterioventral paraventricular nucleus, a system that regulates GnRH. The results of a cross-fostering study provide evidence for a direct effect of postnatal maternal care as well as a possible prenatal influence. Indeed, we found evidence for increased fetal testosterone levels at embryonic day 20 in the female fetuses of High compared to Low LG mothers. Finally, the female offspring of Low LG mothers showed accelerated puberty compared to those of High LG mothers. These data suggest maternal effects in the rat on the development of neuroendocrine systems that regulate female sexual behaviour. Together with studies revealing a maternal effect on the maternal behavior of the female offspring, these findings suggest that maternal care can program alternative reproductive phenotypes in the rat through regionally-specific effects on ER? expression.
Cameron, Nicole; Del Corpo, Adina; Diorio, Josie; McAllister, Kelli; Sharma, Shakti; Meaney, Michael J.
Behavioral and hormonal changes in female naked mole-rats (Heterocephalus glaber) following removal of the breeding female from a colony.
Colonies of naked mole-rats (Heterocephalus glaber) contain a single dominant, breeding female, or "queen", which suppresses reproduction in subordinate females. In this study, the queen and breeding male were removed from a colony at Brookfield Zoo. We examined behavioral and endocrine changes in the remaining colony females. Behavioral observations were conducted weekly and urine samples were collected beginning 3 months prior to the planned removal of animals. Prior to the removal, only the queen displayed the high frequencies of aggressive shoving typical of breeding females. In the first 2 months following removal of the queen, three non-breeding females markedly increased their frequencies of shoving. Urinary progesterone showed that one of three females had probably ovulated both before and after queen removal. Histological examination following fatal agonistic interactions confirmed ovulatory function in two of these three females. Similar behavioral and endocrinological results were obtained for three more females, following the combat deaths of the first three females. These findings suggest that ovarian activation facilitates intrasexual aggression in female naked mole-rats and might contribute to attainment of breeding status. PMID:7557925
Margulis, S W; Saltzman, W; Abbott, D H
[Relationship of fetal hind limb and fetal liver on amino acid metabolism in pregnant rats].
A tracer technique for injections into rat fetal abdomen in utero was employed to obtain a better knowledge of amino acid metabolism in fetal hind limb and fetal liver. Calculation of tissue fluid distribution via 3H-inulin space made possible an estimation of the fetal hind limb and fetal liver intracellular amino acid concentration based upon the fetal plasma and fetal tissue amino acid concentration. A significant concentration gradient between fetal plasma and fetal hind limb was found for glutamate (37.3) but not for alanine (9.7) or leucine (3.0). The radioactivity of fetal hind limb and fetal liver after the injection of 1 microCi of radioactive 14C-glutamate 14C-alanine or 14C-leucine into fetal abdomen was measured. In fetal hind limb, significant radioactivity was recognized after 14C-alanine administration, but not after 14C-glutamate administration as against the significant concentration gradient. However, in fetal liver, significant radioactivity was recognized after 14C-glutamate administration, but not after 14C-alanine administration. We concluded that in fetus, glutamate was released from the hind limbs and a large amount taken up by fetal liver. PMID:3611868
Kyuma, M; Tsuji, Y; Iioka, H; Moriyama, I; Ichijo, M
Effect of 6-mercaptopurine on /sup 65/Zn distribution in the pregnant rat
The effect of 6-mercaptopurine (6-MP) on the distribution of gavaged /sup 65/Zn in maternal and embryonic tissues of Sprague-Dawley rats was examined 24 hr after injection of the drug on day 13 of pregnancy. 6-MP injection resulted in a significantly higher retention of counts of /sup 65/Zn in maternal liver and lower counts in maternal plasma, uterus, placenta, and embryo than in controls. Compared to controls, gel chromatography of maternal liver from 6-MP injected dams showed higher counts associated with a protein peak of molecular weight 6,000-8,000, the approximate molecular weight of the zinc-binding protein metallothionein. These results support the idea that the zinc deficiency, which is observed in day 21 fetuses from dams injected with 6-MP during midgestation, may be the result of a drug-induced sequestering of zinc into maternal liver followed by a decrease in maternal plasma zinc and subsequent reduction in fetal zinc uptake. We suggest that this 6-MP-associated redistribution of zinc into maternal liver may be due to induction of maternal metallothionein synthesis by the drug.
Amemiya, K.; Hurley, L.S.; Keen, C.L.
Serum levels of LH, FSH, estradiol and progesterone in female rats experimentally infected by Trypanosoma evansi.
The goal of this study was to evaluate reproductive hormones in sera samples of female rats experimentally infected by Trypanosoma evansi during different phases of the estrous cycle. For that, 64 animals were divided into two groups: 24 rats for the control group (uninfected), and 40 animals were infected by T. evansi. These groups were divided into subgroups according to the time of infection (days 5 and 15 post-infection; PI) and the phase of the estrous cycle (proestrus, estrus, metestrus and diestrus). Serum was collected at days 5 and 15 PI and the levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), progesterone and estradiol were assessed by enzyme immunoassay technique. The concentration of nitrite/nitrate (NOx), advanced oxidation protein products (AOPP), and thiobarbituric acid reactive substances (TBARS) were measured in ovaries and uteruses in these same periods. Infected females showed significant decrease (P<0.05) of LH, FSH, estradiol and progesterone in different periods and phases of the estrous cycle when compared to uninfected rats. In addition, it was observed an increase in the concentration of NOx, AOPP, and TBARS in the ovaries, which is indicative of cell damage. Therefore, our experimental study showed that T. evansi infection in female rats may cause changes in LH, FSH, estradiol, and progesterone levels regardless of the time of infection or phase of the estrous cycle. PMID:23816642
Faccio, Luciana; Da Silva, Aleksandro S; Tonin, Alexandre A; França, Raqueli T; Gressler, Lucas T; Copetti, Maíra M; Oliveira, Camila B; Sangoi, Manuela B; Moresco, Rafael N; Bottari, Nathieli B; Duarte, Marta M M F; Monteiro, Silvia G
Anti-fertility effects of different fractions of Anethum graveolens L. extracts on female rats.
Our previous studies showed the effects of aqueous and ethanol extracts of Anethum graveolens L. (dill) on female infertility. In the present study we investigated whether different fractions of this herb extract can cause infertility in rats. Female rats were divided into the control groups, the groups receiving either a low (0.5 g/kg)) or a high dose (5g/kg) of water, N-butanol, chloroform and ether fractions of the aqueous plant extract, and the groups receiving either a low (0.045 g/kg) or a high dose (0.45 g/kg) of the same fractions of ethanol extract. The mentioned doses were gavaged in 1mL for 10 days. Vaginal smears were prepared daily. Estradiol and progesterone levels were measured. The left oviduct and ovary were removed, their tissue subsequently being prepared in form of histology slides and stained using haematoxylin-eosin and Masson's trichrome. Female rats assigned to each group were mated with males; after that, crown-rump lengths and weights of newborn rats were measured. Results showed that each fraction produced some changes such as hormonal level reduction (chloroform fraction), diestrus phase prolongation and infertility (water fraction), and increase in pregnancy duration (chloroform and ether fractions). We concluded that each fraction comprises only some of the mentioned components and therefore recommended the usage of crude extract, especially the aqueous one, in case infertility aims to be induced. PMID:23983364
Malihezaman, Monsefi; Mojaba, Masoudi; Elham, Hosseini; Farnaz, Gramifar; Ramin, Miri
Male rats transmit Brucella abortus biotype 1 through sexual intercourse.
The aim of this study was to evaluate transmission of Brucella abortus biotype 1 via sexual intercourse in rats. Male and female virgin Sprague-Dawley (SD) rats were experimentally infected intraperitoneally with 1×10(9)colony forming units (CFU) of B. abortus biotype 1, a Korean bovine isolate. At 14 days after infection, infected male rats (n=10) were housed with uninfected female rats (n=10) and infected female rats (n=10) were housed with uninfected male rats (n=10) for a period of one month. During this period all uninfected female rats became pregnant and 6 of 10 infected female rats became pregnant. Serum from two out of 10 female uninfected rats had positive reactions in the Rose Bengal Plate Agglutination Test (RBPAT), Tube Agglutination Test (TAT) or the Enzyme-Linked Immunosorbent Assay (ELISA); whereas none of the uninfected male rat had positive reactions in these tests. Using bacteriological culture and AMOS-PCR assay, B. abortus biotype 1 was isolated and identified from two uninfected female rats and all of the uninfected male rats were found negative for B. abortus biotype 1. It was concluded that transmission of B. abortus biotype 1 from infected male to uninfected female rats resulted from sexual intercourse. PMID:23664185
Islam, Md Ariful; Khatun, Mst Minara; Baek, Byeong-Kirl
Proteomic changes in female rat hippocampus following exposure to a terrified sound stress.
Stress plays a profound role in the onset of affective disorders, including an elevation in risk factors for depression and anxiety. Women are twice as vulnerable to stress as men because of greater sensitivity to a substance produced during times of anxiety. To better define the abnormal proteins implicated in cognitive deficits and other stress-induced dysfunction, female rats were exposed to terrified sound stress, and two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) were utilized to determine the differential protein expression in the hippocampus in sound-stressed female rats compared with controls. Quantitative differences were found in 44 protein spots which were differentially expressed between the stressed and control groups (fold change of >2; p?0.01). Eighteen protein spots were downregulated, and 26 protein spots were upregulated in the stressed group. The seven most differentially expressed proteins were identified and validated as follows: dihydropyrimidinase-related protein 2 (DRP-2), creatine kinase B type, dynamin-1 protein, alpha-internexin, glial fibrillary acidic protein beta, gamma-enolase, and peptidyl-prolyl cis-trans isomerase A. Changes in protein levels were detected in the hippocampus of female rats subjected to terrified sound stress. The findings herein may open new opportunities for further investigations on the modulation induced in the hippocampus by stress at the molecular level, especially with respect to females stress. PMID:24510750
Yang, Juan; Hu, Lili; Song, Tusheng; Liu, Yong; Wu, Qiuhua; Zhao, Lingyu; Liu, Liying; Zhao, Xiaoge; Zhang, Dianzeng; Huang, Chen
Neuroprotective effects of testosterone on dendritic morphology following partial motoneuron depletion: Efficacy in female rats
Motoneuron loss is a significant medical problem, capable of causing severe movement disorders and even death. We have previously demonstrated that partial depletion of motoneurons induces dendritic atrophy in remaining motoneurons, with a concomitant reduction in motor activation. Treatment of male rats with testosterone attenuates the regressive changes following partial motoneuron depletion. To test whether testosterone has similar effects in females, we examined potential neuroprotective effects in motoneurons innervating muscles of the quadriceps of female rats. Motoneurons were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Simultaneously, some saporin-injected rats were given implants containing testosterone or left untreated. Four weeks later, surviving motoneurons were labeled with cholera toxin-conjugated HRP, and dendritic arbors were reconstructed in 3 dimensions. Compared to normal females, partial motoneuron depletion resulted in decreased dendritic length in remaining quadriceps motoneurons, and this atrophy was greatly attenuated by testosterone treatment. These findings suggest that testosterone has neuroprotective effects on morphology in both males and females, further supporting a role for testosterone as a neurotherapeutic agent in the injured nervous system.
Wilson, Randall E.; Coons, Kellie D.; Sengelaub, Dale R.
The response of Dahl salt-sensitive and salt-resistant female rats to a space flight model
NASA Technical Reports Server (NTRS)
Vitamin D metabolism in the Dahl salt-sensitive (S) rat, a model of salt-induced hypertension, differs from that in the Dahl salt-resistant (R) rat. We have tested the hypothesis that differences in vitamin D metabolism would render the Dahl S rat more susceptible than the Dahl R rat to the effects of a space flight model. Dahl female rats were tail suspended (hind limb unloaded) for 28 days, while fed a low salt (3 g/kg sodium chloride) diet. Plasma 25-OHD concentrations of S rats were significantly lower than that of R rats. Plasma 1,25-(OH)2D concentration was 50% lower in unloaded than in loaded S rats, but was unaffected in unloaded R rats. The left soleus muscle weight and breaking strength of the left femur (torsion test) were 50% and 25% lower in unloaded than in loaded S and R rats. The mineral content of the left femur, however, was significantly lower (by 11%) only in unloaded S rats. We conclude that female S rats are more vulnerable than female R rats to decreases in plasma 1,25-(OH)2D concentration and femur mineral content during hind limb unloading, but equally vulnerable to muscle atrophy and reduced breaking strength of the femur.
Thierry-Palmer, Myrtle; Cephas, Stacy; Cleek, Tammy; Sayavongsa, Phouyong; Arnaud, Sara B.
Prior exercise training does not prevent acute cardiac alterations after myocardial infarction in female rats
OBJECTIVE: This study aimed to investigate whether previous exercise training could prevent or attenuate acute cardiac alterations after myocardial infarction. METHODS: Female rats were submitted to swim training (1 h/day; 5 days/week) or allowed to remain sedentary for 8 weeks. Afterwards, they were randomly assigned to left coronary artery occlusion or sham surgery. After this procedure, the rats remained sedentary for one week until euthanasia. Cardiac structural and functional analyses were performed using Doppler echocardiography. The rats that had a moderate or large infarct size were included in the evaluations. The data (mean ± SEM) were analyzed using a two-way ANOVA model followed by Tukey's post-hoc test. RESULTS: After the surgery, no significant difference between the exercise and sedentary groups was observed in the left ventricular infarct sizes (34.58±3.04 vs. 37.59±3.07). In another group of rats evaluated with Evans blue 1 h after myocardial infarction, no siginificant difference in the area at risk was observed between the exercised and sedentary rats (49.73±1.52 vs. 45.48±3.49). The changes in the left ventricular fractional areas for the exercised and sedentary myocardial infarction groups (36±2% and 39±3%, respectively) were smaller than those for the exercise sham surgery (ES, 67±1%) and sedentary sham surgery (SS, 69±2%) groups. The E/A was higher in the sedentary myocardial infarction (4.4±0.3) and exercised myocardial infarction (5.5±0.3) rats than in the SS (2.4±0.1) and ES (2.2±0.1) rats. CONCLUSION: Previous swim training of female rats does not attenuate systolic and diastolic function alterations after myocardial infarction induced by left coronary artery occlusion, suggesting that cardioprotection cannot be provided by exercise training in this experimental model.
Veiga, Eduardo C A; Antonio, Ednei L; Bocalini, Danilo S; Murad, Neif; Abreu, Luiz C; Tucci, Paulo J F; Sato, Monica A
Effects of Hypergravity Exposure on Plasma Oxytocin (OT) Concentrations in Pregnant and Lactating Rat Dams
NASA Technical Reports Server (NTRS)
From pregnancy to weaning there is a progressive elevation of plasma oxytocin (OT) levels associated with nursing activity, irrespective of litter size. In the present study, we analyzed the effects of continuous 1.5G, 1.75G and 2.0G hypergravity exposure on OT plasma concentration in prepartum (Gestation Day 20) (G20) and lactating (Postnatal day) (P10) rat dams. For this study, litter size was controlled with a yoking procedure established in our lab where individual control litters were yoked-matched to individual hypergravity litters. We reviewed all data at hypergravity irrespective of gravitational level and compared the values with the controls in both G20 (HG, n=15;SC, n=9) and P10 (HG, n=21;SC, n=16). Results showed that over time, we did observe the expected OT increase in both groups. In G20 dams, measurement of OT concentrations showed no significance. However, at P10, measurements of OT concentrations suggest a reduction of about 20% compared to established controls in our laboratory, 0.9+/-0.09 ng/ml for the controls and 0.7+/-0.06 ng/ml for centrifuged animals (p<0.02). These data suggest that exposure to centrifugation may reduce OT levels during lactation. When these plasma samples were obtained, the dams were removed from the litters, and values were not adjusted for the size of the litters. The reduction in OT with centrifugation may reflect a decrease in nursing activity or a decreased responsiveness of the mammary hypothalamic axis. In addition, we have analyzed data on plasma prolactin concentrations and mammary gland development, which may give additional insight to the results of our OT measurements.
Baer, Lisa A.; Wade, Charles E.; Plaut, Karen; Ronca, April E.; Dalton, Bonnie (Technical Monitor)
Effects of di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-ovarian axis in adult female rats.
Di-(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, is widely present in the environment and some products with phthalate plasticizer. It has become a serious problem in recent years. The effect of DEHP on female reproductive system is still not well-studied. This study was to investigate the effects of DEHP on hypothalamus-pituitary-ovarian axis in adult female rats. Compared with control rats, the DEHP-treated rats showed: (1) lower body weight; (2) lower organ coefficient of ovary; (3) higher GnRH level in the hypothalamus; (4) higher mRNA and protein levels of GnRHR in the pituitary; and (5) lower serum sex hormone levels. Our data reveal that DEHP exposure may lead to the disruption of estrogen biosynthesis pathways in female rats and imbalance of hypothalamus-pituitary-ovarian axis. DEHP may impose negative influence on the development and function of the reproductive system in female rats. PMID:24675100
Liu, Te; Li, Na; Zhu, Jian; Yu, Guangyan; Guo, Kun; Zhou, Liting; Zheng, Dongchun; Qu, Xiaofeng; Huang, Jian; Chen, Xin; Wang, Shuyue; Ye, Lin
Effects of high frequency noise on female rat's multi-organ histology.
To investigate the pathological damage of high-frequency stable noise exposure on the brain, heart, liver, and spleen of female rat's. Controlled animal intervention study. Twenty female Sprague-Dawley rats were randomly divided into experimental and control groups with 10 rats in each group. Rats in the experimental group were exposed to continuous high-frequency stable noise for 2 weeks (3 h/day)followed by the pathological damages in the rat's brain, heart, liver, and spleen were compared with those of the control group. After 2 weeks' continuous exposure to high-frequency stable noise, compared with the control group, the most prominent histopathologic changes in the brain tissue structures of the experimental group included loose disorder, hyperemia, edema, blood vessels expand, glial cell hyperplasia, mild atypia in some areas (hyperchromatic nuclei, irregular karyotype), and no degeneration and necrosis. There were dilatation and congestion of central vein, hepatic sinus, and interlobular veins of liver tissue. The structure of hepatic lobule was destroyed by inflammatory cell infiltration, as well as lymphoid nodule formation. There was hyperemia in spleen, but the structure was clear. There was extravasated blood, and the splenic sinuses were highly expanded by a blood clot. Hyperplasias of the lymphoid of white pulp were also active. There was dilation and congestion in myocardial interstitial vascular, and there was mild degeneration and hyperemia in myocardial cells. No hemorrhage and myocardial necrosis were observed. High-frequency stable noise can cause pathological damage in brain, liver, spleen, and heart tissues of female rat at a various degree. PMID:25033787
Xue, Laijun; Zhang, Dajun; Wang, Ting; Shou, Xi
Ethanol consumption in the female Long-Evans rat: a modulatory role of estradiol.
The examination of various gonadal hormone manipulations on ethanol intake in human subjects and in rodent models has resulted in disparate findings. In the present study, we examined the effects of ovariectomy and subsequent estradiol (E(2)) replacement on ethanol intake in a within-subject design, as well as assessed the relevance of reproductive status on the efficacy of an E(2) stimulus in eliciting consumption. Female Long-Evans rats (n = 24) were given access to 10% ethanol and water in a continuous-access paradigm. After establishment of baseline intake values, rats were divided into four groups: sham/placebo (Shm+P), sham/estradiol (Shm+E(2)), ovariectomized/placebo (Ovx+P), and ovariectomized/estradiol (Ovx+E(2)). Rats in the Ovx+P group were found to have a large and permanent decline in ethanol intake that persisted more than 3 months postsurgery. Administration of E(2) to Ovx+E(2) rats was associated with restoration of ethanol consumption to baseline levels. When Shm+E(2) and Ovx+E(2) groups were compared, reproductive status was found to be a determining factor in the efficacy of E(2) to elicit ethanol intake. Together, these findings provide evidence that ovarian hormones, particularly estradiol, exert activational effects on estrogen-responsive substrates to modulate ethanol consumption in the adult female rat. PMID:12007585
Ford, Matthew M; Eldridge, J Charles; Samson, Herman H
Seizure susceptibility in intact and ovariectomized female rats treated with the convulsant pilocarpine.
Despite numerous neuroendocrinological studies of seizures, the influence of estrogen and progesterone on seizures and epilepsy remains unclear. This may be due to the fact that previous studies have not systematically compared distinct endocrine conditions and included all relevant controls. The goal of the present study was to conduct such a study using pilocarpine as chemoconvulsant. Thus, age and weight-matched, intact or ovariectomized rats were tested to determine incidence of status epilepticus and to study events leading to status. Intact female rats were sampled at each cycle stage (proestrus, estrus, metestrus, or diestrus 2). Convulsant was administered at the same time of day, 10:00-10:30 a.m. Statistical analysis showed that there was a significantly lower incidence of status on the morning of estrus, but differences were attenuated in older animals. Ovariectomized rats were distinct in their rapid progression to status. These results show that the incidence of status in female rats following pilocarpine injection, and the progression to pilocarpine-induced status, are influenced by reproductive state as well as age. The hormonal milieu present specifically on the morning of estrus appears to decrease susceptibility to pilocarpine-induced status, particularly at young ages. In contrast, the chronic absence of reproductive steroids that characterizes the ovariectomized rat leads to a more rapid progression to status. This dissociation between incidence vs. progression provides new insight into the influence of estrogen and progesterone on seizures. PMID:16084511
Scharfman, Helen E; Goodman, Jeffrey H; Rigoulot, Marie-Aude; Berger, Russell E; Walling, Susan G; Mercurio, Thomas C; Stormes, Kerry; Maclusky, Neil J
Urethral compensatory mechanisms to maintain urinary continence after pudendal nerve injury in female rats
Introduction and hypothesis To investigate the urethral compensatory mechanisms to maintain urinary continence after pudendal nerve injury. Methods In naive, acute pudendal nerve transection (PNT) and 4 weeks after PNT (PNT-4w) female rats, leak point pressures (LPPs) during bladder compression were measured before and after the application of hexamethonium (C6), propranolol and N?nitro-L-arginine methyl ester (L-NAME), or terazosin and atropine. Responses to carbachol and phenylephrine of proximal and middle urethral muscle strips from naive and PNT-4w rats were also examined. Results LPPs were significantly decreased in PNT rats but not in PNT-4w rats. LPPs in PNT rats were significantly increased by C6 or L-NAME while LPPs in PNT-4w rats were significantly decreased by C6, or terazosin and atropine. Excitatory responses to carbachol and phenylephrine in the proximal urethral muscle were significantly larger in PNT-4w rats. Conclusions These results suggest that ?1-adrenoceptor and muscarinic receptor-mediated contractility is upregulated in the proximal urethra 4 weeks after PNT.
Furuta, Akira; Suzuki, Yasuyuki; Asano, Koji; de Groat, William C.; Egawa, Shin; Yoshimura, Naoki
Cortical NR2B NMDA subunit antagonism reduces inflammatory pain in male and female rats
Background Studies have shown that N-methyl-D-aspartate (NMDA) receptors play a critical role in pain processing at different levels of the central nervous system. Methods In this study, we used adult Wistar rats to examine gender differences in the effects of NR2B NMDA antagonism at the level of the anterior cingulate cortex in phasic pain, and in the first and second phases of a formalin test. Rats underwent stereotactic surgery for cannula implantation in the anterior cingulate cortex. After recovery, paw withdrawal latency to a noxious thermal stimulus was assessed. Rats were also subjected to a formalin pain test whereby 60 ?L of 5% formalin was injected into the right hind paw. Results Female and male rats that received Ro 25-6981, an NR2B antagonist, before formalin injection showed significantly reduced pain responses to the formalin test compared with saline-injected control rats (P < 0.05). No gender differences in phasic pain responses were found in rats treated with Ro 25-6981. Conclusion These results suggest that cortical antagonism of the NR2B subunit reduces inflammatory pain levels in both genders of rat.
Quintero, Gabriel C; Herrera, Jairo; Bethancourt, Jose
Prolactin regulates kisspeptin neurons in the arcuate nucleus to suppress LH secretion in female rats.
Prolactin (PRL) is known to suppress LH secretion. Kisspeptin neurons regulate LH secretion and express PRL receptors. We investigated whether PRL acts on kisspeptin neurons to suppress LH secretion in lactating (Lac) and virgin rats. Lac rats displayed high PRL secretion and reduced plasma LH and kisspeptin immunoreactivity in the arcuate nucleus (ARC). Bromocriptine-induced PRL blockade significantly increased ARC kisspeptin and plasma LH levels in Lac rats but did not restore them to the levels of non-Lac rats. Bromocriptine effects were prevented by the coadministration of ovine PRL (oPRL). Virgin ovariectomized (OVX) rats treated with either systemic or intracerebroventricular oPRL displayed reduction of kisspeptin expression in the ARC and plasma LH levels, and these effects were comparable with those of estradiol treatment in OVX rats. Conversely, estradiol-treated OVX rats displayed increased kisspeptin immunoreactivity in the anteroventral periventricular nucleus, whereas oPRL had no effect in this brain area. The expression of phosphorylated signal transducer and activator of transcription 5 was used to determine whether kisspeptin neurons in the ARC were responsive to PRL. Accordingly, intracerebroventricular oPRL induced expression of phosphorylated signal transducer and activator of transcription 5 in the great majority of ARC kisspeptin neurons in virgin and Lac rats. We provide here evidence that PRL acts on ARC neurons to inhibit kisspeptin expression in female rats. During lactation, PRL contributes to the inhibition of ARC kisspeptin. In OVX rats, high PRL levels suppress kisspeptin expression and reduce LH release. These findings suggest a pathway through which hyperprolactinemia may inhibit LH secretion and thereby cause infertility. PMID:24456164
Araujo-Lopes, Roberta; Crampton, Jessica R; Aquino, Nayara S S; Miranda, Roberta M; Kokay, Ilona C; Reis, Adelina M; Franci, Celso R; Grattan, David R; Szawka, Raphael E
Differentiation in boron distribution in adult male and female rats' normal brain: a BNCT approach.
Boron distribution in adult male and female rats' normal brain after boron carrier injection (0.005 g Boric Acid+0.005 g Borax+10 ml distilled water, pH: 7.4) was studied in this research. Coronal sections of control and trial animal tissue samples were irradiated with thermal neutrons. Using alpha autoradiography, significant differences in boron concentration were seen in forebrain, midbrain and hindbrain sections of male and female animal groups with the highest value, four hours after boron compound injection. PMID:22484141
Goodarzi, Samereh; Pazirandeh, Ali; Jameie, Seyed Behnamedin; Khojasteh, Nasrin Baghban
Influence of ovarian hormones on development of ingestive responding to alterations in fatty acid oxidation in female rats
Adult male rats have been demonstrated to increase food intake in response to administration of drugs that interfere with oxidation of fatty acids (e.g. methyl palmoxirate and mercaptoacetate [MA]), effects that are larger in animals maintained on a high-fat diet. In contrast, while administration of MA has been reported to stimulate food intake in pre-pubertal female rats, food intake is not stimulated by MA in adult female rats. Instead, administration of MA to adult females results in changes in reproductive behavior and physiology. The present experiments were designed to examine the effects of administration of MA on food intake in adult female rats. The results demonstrated that, as previously reported, food intake was stimulated by MA in adult male rats on low-fat and high-fat diets, but food intake in was not stimulated by MA in gonadally-intact adult female rats on either low-fat or high-fat diet. Further, MA did not stimulate food intake in female rats ovariectomized as adults. However, when females were ovariectomized prior to the onset of puberty (postnatal day 25 – 28), food intake was stimulated by administration of MA in adulthood. Finally, cyclic injections of 17-?-estradiol benzoate given to females ovariectomized prior to the onset of puberty abolished the stimulatory effects of MA on food intake in adult females. Taken together, the data suggest that exposure to estrogens during the time of puberty in female rats can persistently alter adult ingestive responding to signals related to changes in energy utilization.
Swithers, Susan E.; McCurley, Melissa; Hamilton, Erica; Doerflinger, Alicia
Unit: Males and Females, Inspection Pack, National Trial Print.
ERIC Educational Resources Information Center
This is a National Trial Print of an Australian Science Education Project unit entitled Males and Females. Materials provided consist of a teacher's edition of the written materials, a student record book, and seven large black and white photographs showing various stages in the dissection of a pregnant rat. This unit has been written to help…
Australian Science Education Project, Toorak, Victoria.
Pharmacological modulation of the endocannabinoid signalling alters binge-type eating behaviour in female rats
Background and Purpose Binge eating disorder (BED) is characterized by excessive food intake during short periods of time. Recent evidence suggests that alterations in the endocannabinoid signalling could be involved in the pathophysiology of BED. In this study, we investigated whether pharmacological manipulation of endocannabinoid transmission may be effective in modulating the aberrant eating behaviour present in a validated rat model of BED. Experimental Approach Binge-type eating was induced in female rats by providing limited access to an optional source of dietary fat (margarine). Rats were divided into three groups, all with ad libitum access to chow and water: control (C), with no access to margarine; low restriction (LR), with 2 h margarine access 7 days a week; high restriction (HR), with 2 h margarine access 3 days a week. Key Results Compared with the LR group, the HR group consumed more margarine and this was accompanied by an increase in body weight. The cannabinoid CB1/CB2 receptor agonist ?9-tetrahydrocannabinol significantly increased margarine intake selectively in LR rats, while the fatty acid amide hydrolase inhibitor URB597 showed no effect. The CB1 receptor inverse agonist/antagonist rimonabant dose-dependently reduced margarine intake in HR rats. Notably, in HR rats, chronic treatment with a low dose of rimonabant induced a selective long-lasting reduction in margarine intake that did not develop tolerance, and a significant and persistent reduction in body weight. Conclusions and Implications Chronic pharmacological blockade of CB1 receptors reduces binge eating behaviour in female rats and may prove effective in treating BED, with an associated significant reduction in body weight. Linked Articles This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-4 & http://dx.doi.org/10.1111/bph.2012.167.issue-8
Scherma, M; Fattore, L; Satta, V; Businco, F; Pigliacampo, B; Goldberg, SR; Dessi, C; Fratta, W; Fadda, P
Bradykinin B2 receptor-dependent enhancement of enalapril-evoked hypotension in ethanol-fed female rats.
Our previous studies showed that chronic ethanol feeding attenuates centrally (clonidine) evoked and potentiates peripherally (hydralazine) evoked hypotension in female rats. In this study, we investigated whether chronic ethanol (8 weeks, 5% wt/vol) alters hemodynamic responses elicited by angiotensin-converting enzyme (ACE) inhibition (enalapril) in telemetered female rats. Given the intimate interaction between ACE and bradykinin, studies were extended to investigate the role of bradykinin receptor (B2R) in ethanol-enalapril interaction. Compared with pair-fed controls, ethanol-fed female rats exhibited (1) higher renal expressions of ACE and B2R proteins and angiotensin II levels and (2) lower blood pressure. Pharmacological inhibition of ACE and B2R supports functional role for the higher levels of these 2 proteins in ethanol-fed rats because enalapril (10 mg/kg, intraperitoneally) caused significantly greater hypotensive response in ethanol-fed rats than in control rats. Further, blockade of B2R with bradyzide (2 mg/kg, intraperitoneally) abrogated the enhanced hypotensive effect of enalapril in ethanol-fed rats but had no effect on enalapril-evoked hypotension in control rats. Finally, enalapril enhancement of spontaneous baroreflex sensitivity (BRS) in control was absent in ethanol-fed rats. These findings demonstrate that chronic ethanol produces B2R-dependent enhancement of the hypotensive response elicited by enalapril and abrogates enalapril-evoked enhancement of spontaneous baroreflex response in female rats. PMID:20966761
El-Mas, Mahmoud M; Abdel-Rahman, Abdel A
Alteration of the Cardiac Sympathetic Innervation Is Modulated by Duration of Diabetes in Female Rats
To evaluate the sympathetic innervation of the female diabetic heart, resting heart rate and sympathetic tone were assessed in vivo, and effect of tyramine on spontaneous beating rate, norepinephrine atrial concentrations, uptake, and release were determined in vitro in streptozotocin- (STZ-) treated rats and respective controls aged 3 months to 2 years. Resting bradycardia, decreased sympathetic tone, deceleration of spontaneous beating rate, and slightly declining carrier-mediated, but preserved exocytotic norepinephrine release from the atria were found in younger diabetic rats while the reactivity of the right atria to tyramine was not affected with age and disease duration. Diabetic two-year-old animals displayed symptoms of partial spontaneous recovery including normoglycemia, increased plasma insulin concentrations, fully recovered sympathetic tone, but putative change, in releasable norepinephrine tissue stores. Our data suggested that female diabetic heart exposed to long-lasting diabetic conditions seems to be more resistant to alteration in sympathetic innervation than the male one.
Sviglerova, Jitka; Mudra, Jiri; Tonar, Zbynek; Slavikova, Jana; Kuncova, Jitka
Acute reproductive toxicity of 3,3'-iminodipropionitrile in female rats.
A potent neurotoxin 3,3'-iminodipropionitrile (IDPN), which is an occupational exposure hazard in industry, induces persistent behavioral abnormalities in experimental animals; however, its reproductive toxicity has not been determined. Therefore, we assessed the toxicity of IDPN in the reproductive system of female rats. A single intraperitoneal injection of IDPN (1000 mg/kg body weight) into female Wistar-Imamichi rats caused acute estrous cycle arrest at diestrus for up to 15 days. The arrest was accompanied by follicular atresia, and following arrest, the estrous cycle and ovarian morphology recovered. Ovarian mRNA levels of growth differentiation factor 9 and Fas ligand, a cell death marker, transiently increased following IDPN injection, but eventually they returned to basal levels. IDPN added to in vitro cultures of ovarian follicles also induced the expression of these genes, indicating that IDPN directly promoted ovarian cell death. PMID:22074697
Takahashi, Noriyuki; Tarumi, Wataru; Ishizuka, Bunpei
Humoral (immunological) responses in female albino rats during rotating magnetic field exposures
NASA Astrophysics Data System (ADS)
Experiments were designed to evaluate the primary and secondary humoral responses to a rotating magnetic field configuration, which is known to evoke significant biobehavioral changes. Ten days after inoculation with human serum albumin and 10 days before a booster, female rats were exposed to eigher a 0.5 Hz rotating magnetic field (RMF) or to room conditions (control). The lighting schedule was either continuous or involved a light-dark cycle (LD) of 12:12h. A third group of rats served as colony room controls. Group differences of low statistical significance were found when females were exposed to continuous lighting rather than the LD 12:12 light-dark cycle. However, the effects were considered trivial and not sufficient to explain the previously reported biobehavioral changes evoked by this field configuration.
Reid, K.; Falter, H.; Persinger, M. A.
Effects of tetrabenazine on lordosis behaviour and on brain monoamines in the female rat
Summary The time course of action of tetrabenazine (TBZ), 2 and 10 mg\\/kg i.p., on lordosis behaviour and on brain monoamines in ovariectomized estrogen pretreated female rats, was studied. The administration of TBZ (2 mg\\/kg) produced a decrease in brain DA and an increase in the number of lordosis, whereas 10 mg\\/kg of TBZ resulted in the same increase in
S. Ahlenius; J. Engel; H. Eriksson; P. Södersten
Effects of Estrogen Antagonists and Agonists on the ACTH Response to Restraint Stress in Female Rats
Previous studies have found that female rats are less sensitive than males to hypothalamic-pituitary-adrenal axis feedback inhibition by exogenous glucocorticoid administration. To determine whether estrogen contributes to this sex difference, we examined the effects of the estrogen antagonists tamoxifen and C1628 on the ACTH and corticosterone responses to restraint stress. CI628 increased both the ACTH and corticosterone response to restraint
Elizabeth A Young; Margaret Altemus; Valerie Parkison; Savitha Shastry
Threshold of Adulthood for the Onset of Nicotine Self-Administration in Male and Female Rats
The great majority of tobacco addiction begins during adolescence. More heavily addicted smokers begin smoking earlier, but differentiating the neurobehavioral impact of nicotine self-administration during adolescence from self-selection bias (whereby people more prone to heavy addiction also begin earlier) cannot be ethically unconfounded in humans. The goals of this research were to determine the age threshold for the adult-like nicotine self-administration and determine sex differences. Male and female Sprague-Dawley rats were tested for nicotine self-administration starting at 4, 5, 6, 7, and 8 weeks of age in an operant FR1 schedule for IV nicotine (0.03 mg/kg/infusion) in 45-minute sessions for two weeks, with one week of enforced abstinence and one week of resumed access. This study replicated our earlier work that nicotine self-administration was increased in adolescent vs. adult rats and that the effect was more pronounced in adolescent males, but the increased nicotine self-administration was more persistent in adolescent-onset females. The age threshold for adult-like behavior was 6–7 weeks of age. Adolescent-onset nicotine self-administration had persisting effects of eggaurated increases of nicotine self-administration when fixed-ratio requirements for self-administration were lowered. Female rats that had begun nicotine self-administration during adolescence showed exaggerated increases in nicotine self-administration after a switch back to FR1 from FR8, indicating a lessened control over their self-administration. Adolescent-onset nicotine self-administration was not found to potentiate cocaine self-administration. Adolescent-onset nicotine self-administration causes persistent increases in nicotine self-administration in female rats even after they reach adulthood and disrupts control over self-administration behavior.
Levin, Edward D.; Slade, Susan; Wells, Corinne; Cauley, Marty; Petro, Ann; Vendittelli, Analise; Johnson, Michael; Williams, Paul; Horton, Kofi; Rezvani, Amir H.
Effect of the Serotoninergic System on Luteinizing Hormone Secretion in Prepubertal Female Rats
The effect of 5-hydroxytryptophan (5-HTP), a serotonin precursor, and p-chloroamphetamine (PCA), a serotonin neurotoxin, selective for serotoninergic neurons, that depletes serotonin (5-HT) levels in brain, on the luteinizing hormone (LH) release response to estrogen-progesterone (E-P) was studied in prepubertal female rats of different ages. E-P decreased LH levels on days 16, 18 and 20, increasing the levels of the pituitary
Jaime A. Moguilevsky; Maria R. Faigón; Pablo Scacchi; Berta Szwarcfarb
Enhancement by Progesterone of 5Hydroxytryptophan Inhibition of the Copulatory Response in the Female Rat
A study was made of the influence of different hormonal treatments used to induce copulatory behavior in ovariectomized female rats (lordosis behavior), on the effects of an endogenous increase of 5-HT or catecholamines achieved by DL-5-HTP and L-Dopa. The lordosis response (LR) has been shown to be inhibited by increased serotonergic and catecholaminergic neuronal activity. The 5-HT agonist lysergic acid
Anni Sietnieks; Bengt J. Meyerson
Influence of Endogenous Leptin Tone on the Estrous Cycle and Luteinizing Hormone Pulsatility in Female Rats
Recent data indicate that leptin may well play an important regulatory role in the hypothalamo-pituitary-gonadal axis. In order to further unravel the mechanisms by which leptin acts, we have studied the effect of treatment (8 days) of leptin antiserum (5 ?l daily; i.c.v.) on LH pulsatility and estrous cycle in adult female rats. The administration of leptin antiserum led to
Eva Carro; Leonor Pinilla; Luisa M. Seoane; Robert V. Considine; Enrique Aguilar; Felipe F. Casanueva; Carlos Dieguez
Hippocampal cell proliferation and spatial memory performance after social instability stress in adolescence in female rats
We investigated the immediate and lasting effect of social instability stress in adolescence [SS: daily 1h isolation and change of cage partner postnatal days (P) 30–45] on cell proliferation in the hippocampus and on spatial memory using an object spatial location (SL) test. Female rats were treated with bromodeoxyuridine (BrdU) P43–45, and on P49, SS had reduced cell hippocampal cell
Cheryl M. McCormick; Feather Nixon; Catherine Thomas; Bobbi Lowie; Joshua Dyck
Early life stress impairs fear conditioning in adult male and female rats
We demonstrated that neonatal isolation (1-h pup isolation; postnatal days 2–9) impairs context-induced fear conditioning in adult male rats and tends to enhance this effect and foot shock sensitivity in females. In this study, we examine the effects of brief (i.e., handling; 15 min) and prolonged (3 h) maternal separations (postnatal days 1–21) on fear conditioning and foot shock sensitivity
Therese A. Kosten; Hongjoo J. Lee; Jeansok J. Kim
Interleukin1 Inhibits Sexual Behavior in Female but Not in Male Rats
The cytokine interleukin-1 (IL-1) is released by a variety of cells in response to infection or injury. IL-1 produces several neuroendocrine and behavioral effects, including a suppression of reproductive functions and goal-directed behaviors. The present study examined the effect of IL-1 on sexual behavior in male and female rats. The following behavioral tests were employed: preference for a sexually appropriate
R. Yirmiya; R. Avitsur; O. Donchin; E. Cohen
Effects of ethanol ingestion and dietary fat levels on mitochondrial lipids in male and female rats
The effects of sex, dietary fat levels, and ethanol ingestion on rat liver mitochondrial lipids have been studied. Two groups\\u000a of male animals were fed either a low-fat diet for about 76 days or a high-fat diet for about 52 days, and two groups of female\\u000a animals were fed the same low-fat diet for about 50 days or the high-fat
John A. Thompson; Ronald C. Reitz
Metabolism of n-Butyl Benzyl Phthalate in the Female Wistar Rat. Identification of New Metabolites
n-Butyl benzyl phthalate (BBP), a plasticizer used in polyvinylchloride (PVC) and other polymers, has been orally administered to female Wistar rats with four doses (150, 475, 780 and 1500mg\\/kg body weight\\/day) for 3 consecutive days. Metabolites recovered in urines were analysed by gas chromatography–mass spectrometry (GC–MS) after 24, 48 and 72 hours. Six metabolites were identified. Mono-n-butyl phthalate (MBuP) and
C Nativelle; K Picard; I Valentin; J. C Lhuguenot; M. C Chagnon
Estrogen Modulates ?1\\/?-Adrenoceptor- Induced Signaling and Melatonin Production in Female Rat Pinealocytes
Nocturnal rise in pineal melatonin output is due to the night-induced acceleration of noradrenergic transmission and ?1- and ?-adrenoceptor activation. In addition, in female animals, cyclic oscillations in circulating levels of sex steroid hormones are accompanied by changes in the rate of pineal melatonin secretion. To investigate whether estrogen directly affects pineal adrenoceptor responsiveness, pinealocytes from 21-day-old ovariectomized rats were
Francisco J. Hernández-Díaz; Juan J. Sánchez; Pedro Abreu; Ignacio López-Coviella; Lucía Tabares; Luis Prieto; Rafael Alonso
A Specific Population of Gonadotrophs Purified from Immature Female Rat Pituitary
When dispersed pituitary cells from 14-day-old female rats were sedimented in a bovine serum albumin gradient, a fraction was isolated which consisted of almost 90 percent of large cells that stained purple in the periodic acid-Schiff (PAS) reaction. Immunostaining indicated that over 85 percent of these PAS-purple cells were gonadotrophs containing both follicle stimulating and luteinizing hormone. Reproducible cell cultures
Carl Denef; Emmy Hautekeete; Lee Rubin
A study of chromium and ethanol toxicity in female Wistar rats
The purpose of this study was to evaluate the interactive toxicity of ethanol (EtOH) with potassium dichromate (K2Cr2O7 ? chromium). Young female Wistar rats (100–105 gms) were divided into four groups of 5 to 6 each were dosed through water 10% EtOH (v\\/v) or 25 ppm chromium or 10% EtOH + 25 ppm chromium for a period of 22 weeks
A. Chopra; G. Pereira; T. Gomes; J. Pereira; P. Prabhu; S. Krishnan; C. V. Rao
Oxytocin Causes a Long-Term Decrease of Blood Pressure in Female and Male Rats
The aim of the present study was to investigate the long-term effects of oxytocin (OXY) on blood pressure (BP) and heart rate (HR) in conscious female and male rats. For this purpose, subcutaneous (SC) (0.01, 0.1, and 1 mg\\/kg) or intracerebroventricular (ICV) (1 ?g\\/kg) injections of OXY were given during 5-day periods. BP and HR were measured daily. A significant
Effect of chronic ethanol consumption in female rats subjected to experimental sepsis
The objective of this research was to evaluate the interference of ethanol consumption by female rats with cytokines involved in the sepsis process and its correlation with mortality, the main outcome of sepsis. Female Wistar rats in estrus phase were evaluated in three experiments. Experiment 1 (n=40) was performed to determine survival rates. Experiment 2 (n=69) was designed for biochemical analysis, measurement of cytokine and estrogen levels before and after sepsis, and experiment 3 (n=10) was performed to evaluate bacterial growth by colony counts of peritoneal fluid. In all experiments, treated animals were exposed to a 10% ethanol/water solution (v/v) as the single drinking source, while untreated animals were given tap water. After 4 weeks, sepsis was induced in the rats by ip injection of feces. In experiment 1, mortality in ethanol-exposed animals was delayed compared with those that drank water (48 h; P=0.0001). Experiment 2 showed increased tumor necrosis factor alpha (TNF-?) and decreased interleukin-6 (IL-6) and macrophage migration inhibitory factor in septic animals exposed to ethanol compared to septic animals not exposed. Sepsis also increased TNF-? and IL-6 levels in both ethanol- and water-exposed groups. Biochemical analysis showed higher creatinine, alanine aminotransferase and aspartate aminotransferase and decreased glucose levels in septic animals that were exposed to ethanol. In experiment 3, septic animals exposed to ethanol showed decreased numbers of colony-forming units than septic animals exposed to water. These results suggest that ethanol consumption delays the mortality of female rats in estrus phase after sepsis induction. Female characteristics, most probably sex hormones, may be involved in cytokine expression.
Castro, C.L.; Aguiar-Nemer, A.S.; Castro-Faria-Neto, H.C.; Barros, F.R.; Rocha, E.M.S.; Silva-Fonseca, V.A.
Triclosan exposure modulates estrogen-dependent responses in the female wistar rat.
Triclosan is an antimicrobial found in personal care and sanitizing products, such as soaps, toothpaste, and hair products. There have been recent concerns for the possible effects on human health, as triclosan has been detected in human breast milk, blood, and urine samples. In a previous study, we found that triclosan alters serum thyroid hormone and testosterone concentrations in male rats. In the current study, we evaluated the effects of triclosan in the female Wistar rat following exposure for 21 days in the Endocrine Disruptor Screening Program pubertal protocol and the weanling uterotrophic assay (3-day exposure). In the pubertal study, triclosan advanced the age of onset of vaginal opening and increased uterine weight at 150 mg/kg, indicative of an estrogenic effect. In the uterotrophic assay, rats received oral doses of triclosan (1.18, 2.35, 4.69, 9.37, 18.75, 37.5, 75, 150, and 300 mg/kg) alone, 3 microg/kg ethinyl estradiol (EE), or triclosan (same doses as above) plus 3 microg/kg EE. Uterine weight was increased in the EE group (positive control) as compared with the control but was not affected by triclosan alone. However, there was a significant dose-dependent increase in the group cotreated with EE and triclosan (>or= 4.69 mg/kg) as compared with EE alone, indicating a potentiation of the estrogen response on uterine weight. This result was well correlated with potentiated estrogen-induced changes in uterine histology. Serum thyroid hormone concentrations were also suppressed by triclosan in this study, similar to other studies in the male and female rat. In conclusion, triclosan affected estrogen-mediated responses in the pubertal and weanling female rat and also suppressed thyroid hormone in both studies. The lowest effective concentrations in the rodent model are approximately 10 (for estrogen) and 40 (for thyroid hormone) times higher than the highest concentrations reported in human plasma. PMID:20562219
Stoker, Tammy E; Gibson, Emily K; Zorrilla, Leah M
Macrophagic and microglial responses after focal traumatic brain injury in the female rat
Background After central nervous system injury, inflammatory macrophages (M1) predominate over anti-inflammatory macrophages (M2). The temporal profile of M1/M2 phenotypes in macrophages and microglia after traumatic brain injury (TBI) in rats is unknown. We subjected female rats to severe controlled cortical impact (CCI) and examined the postinjury M1/M2 time course in their brains. Methods The motor cortex (2.5 mm left laterally and 1.0 mm anteriorly from the bregma) of anesthetized female Wistar rats (ages 8 to 10 weeks; N?=?72) underwent histologically moderate to severe CCI with a 5-mm impactor tip. Separate cohorts of rats had their brains dissociated into cells for flow cytometry, perfusion-fixed for immunohistochemistry (IHC) and ex vivo magnetic resonance imaging or flash-frozen for RNA and protein analysis. For each analytical method used, separate postinjury times were included for 24 hours; 3 or 5 days; or 1, 2, 4 or 8 weeks. Results By IHC, we found that the macrophagic and microglial responses peaked at 5 to 7 days post-TBI with characteristics of mixed populations of M1 and M2 phenotypes. Upon flow cytometry examination of immunological cells isolated from brain tissue, we observed that peak M2-associated staining occurred at 5 days post-TBI. Chemokine analysis by multiplex assay showed statistically significant increases in macrophage inflammatory protein 1? and keratinocyte chemoattractant/growth-related oncogene on the ipsilateral side within the first 24 hours after injury relative to controls and to the contralateral side. Quantitative RT-PCR analysis demonstrated expression of both M1- and M2-associated markers, which peaked at 5 days post-TBI. Conclusions The responses of macrophagic and microglial cells to histologically severe CCI in the female rat are maximal between days 3 and 7 postinjury. The response to injury is a mixture of M1 and M2 phenotypes.
Physiological, biochemical and histological alterations induced by administration of imidacloprid in female albino rats.
Imidacloprid, a neonicotinoid the newest class of major insecticide has outstanding potency and systemic action for crop protection against piercing and sucking insects pests and also highly effective for control of flea on cats and dogs. The effect of oral administration of two doses of imidacloprid 10 and 20mg/kg/day for 60 days on biochemical parameters, histopathology and protein profile of female albino rat was assessed. Average feed intake was significantly reduced (P<0.01) at 20mg/kg/day. Relative weight of heart and spleen decreased significantly (P<0.05) at higher dose level. Non significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), acid phosphatase (ACP), alkaline phosphatase (AKP) activity was observed in both the imidacloprid treated groups. There was significant decrease (P<0.01, P<0.05) in acetyl cholinesterase (AChE) activity in plasma and brain of both the imidacloprid treated groups. Microscopically, liver tissue of rats treated with higher dose of imidacloprid showed marked dilation and congestion of central vein and degeneration of hepatocytes. The exposure to imidacloprid produced histopathological changes that could be correlated with changes in the biochemical profile of female albino rats. The blood plasma proteins were examined by SDS PAGE. There was no diagnostic difference in the pattern of plasma protein profile of control and treated rats. Based on the present physiological, biochemical and histological studies it is evident that imidacloprid did not produce any significant effects at 10mg/kg/day dose but induced toxicological effects at 20mg/kg/day to female rats. PMID:24759051
Vohra, Prerna; Khera, Kuldeep Singh; Sangha, Gurinder Kaur
Salt Loading Promotes Kidney Injury via Fibrosis in Young Female Ren2 Rats
Background/Aims It is increasingly recognized that there is sexual dimorphism in kidney disease progression; however, this disparity is lost in the presence of diabetes where women progress at a similar rate to men. The renin-angiotensin-aldosterone system (RAAS) is known to regulate diabetes-induced kidney injury, and recent literature would suggest that gender differences exist in RAAS-dependent responses in the kidney. In this regard, these gender differences may be overcome by excessive salt intake. Thereby, we hypothesized that salt would promote proteinuria in transgenic female rats under conditions of excess tissue angiotensin (Ang) II and circulating aldosterone. Materials and Methods We utilized young female transgenic (mRen2)27 (Ren2) rats and Sprague-Dawley (SD) littermates and fed a high-salt diet (4%) over 3 weeks. Results Compared to SD and Ren2 controls, female Ren2 rats fed a high-salt diet displayed increases in proteinuria, periarterial and interstitial fibrosis as well as ultrastructural evidence of basement membrane thickening, loss of mitochondrial elongation, mitochondrial fragmentation and attenuation of basilar canalicular infoldings. These findings occurred temporally with increases in transforming growth factor-? but not indices of oxidant stress. Conclusions Our current data suggest that a diet high in salt promotes progressive kidney injury as measured by proteinuria and fibrosis associated with transforming growth factor-? under conditions of excess tissue Ang II and circulating aldosterone.
Habibi, Javad; Hayden, Melvin R.; Ferrario, Carlos M.; Sowers, James R.; Whaley-Connell, Adam T.
Detecting Early Biomechanical Effects of Zoledronic Acid on Femurs of Osteoporotic Female Rats
Aim. To investigate the biomechanical effects of zoledronic acid (ZA) on femurs of female osteoporotic rats after follow-up periods of 9 and 12 months. Methods. Eighty female Wistar rats were prospectively assessed. At 60 days of age, the animals were randomly divided into two groups: bilateral oophorectomy (O) (n = 40) and sham surgery (S) (n = 40). At 90 days of age, groups O and S were randomly subdivided into four groups, according to whether 0.1?mg/kg of ZA or distilled water (DW) was intraperitoneally administered: OZA (n = 20), ODW (n = 20), SZA (n = 20), and SDW (n = 20). The animals were sacrificed at 9 and 12 months after the administration of the substances, and then their right femurs were removed and analyzed biomechanically. Axial compression tests that focused on determining the maximum load (N), yield point (N), and stiffness coefficient (N/mm) of the proximal femur were performed in the biomechanical study. Results. ZA significantly increased the maximum load and yield point, reducing the stiffness coefficient concerning the oophorectomy status and follow-up period. Conclusion. Zoledronic acid, at a dose of 0.1?mg/kg, significantly increased the maximum loads and yield points and reduced the stiffness coefficients in the femurs of female rats with osteoporosis caused by bilateral oophorectomy.
Palacio, Evandro Pereira; Muller, Sergio Swain; Sardenberg, Trajano; Mizobuchi, Roberto Ryuiti; Galbiatti, Jose Antonio; Durigan, Alcides; Savarese, Aniello; Ortolan, Erika Veruska Paiva
Energy Restriction Reduces Bone Density and Biomechanical Properties in Aged Female Rats1,2
Bone mineral density (BMD) is highly correlated with body weight, and weight loss is associated with reduced BMD. Whether such losses of BMD increase skeletal fragility is unclear. We examined the effect of 9 wk of energy restriction (ER) on bone density, mineral and matrix protein composition and biomechanical properties in mature (20 wk old, n = 12) and aged (48 wk old, n = 16) female rats. Energy-restricted rats were fed 40% less energy than controls that consumed food ad libitum. Bone content of mineral (ash and calcium content) and matrix proteins (hydroxyproline, pyridinium crosslinks and proteoglycans), serum hormones, site-specific bone density and biomechanical properties (peak load, peak torque, shear stiffness and bending stiffness) were measured at the conclusion of the study. In both age groups, ER reduced body weight by 15 ± 10% (P < 0.001) and dramatically decreased femoral bone density by 32–35% (P < 0.01) compared with controls. Energy restriction resulted in a small reduction in tibia and humerus density, as well as biomechanical properties in the aged but not mature rats (P < 0.05). Reduced serum levels of insulin and estradiol due to ER in aged rats (P < 0.05) may play a role in altering bone quality. These data show that although weight loss due to ER is detrimental to some bone parameters in mature rats, only aged rats show consistent reductions in bone density and biomechanical properties.
Talbott, Shawn M.; Cifuentes, Mariana; Dunn, Michael G.; Shapses, Sue A.
Protective effect of curcuminoids on age-related mitochondrial impairment in female Wistar rat brain.
The present study demonstrated the neuroprotective effect of curcuminoids, the active polyphenols of Curcuma longa (L.) rhizomes on mitochondrial dysfunctioning in middle aged and aged female Wistar rat brain. Rats were orally treated with curcuminoids (100 mg/kg) for 3 months and their brain was collected for evaluation of mitochondrial enzymes and complexes activity, ultra structural changes in mitochondria, neuronal nitric oxide synthase (nNOS) protein expression, adenosine triphosphate (ATP) and lipofuscin content. Significant alterations were observed in all the tested parameters in highly aged rat brain when compared with young control. Long term curcuminoids administration prevented this age associated loss of mitochondrial enzymes and complexes activity in middle aged rat brain except for malate dehydrogenase, Complex II and IV activity when compared with young control. Among aged rats, curcuminoids treatment specifically elevated isocitrate and NADH dehydrogenase, cytochrome c oxidase, Complex I and total ATP content. A significant down-regulation of nNOS protein expression along with reduced lipofuscin content was also observed in curucminoids treated middle aged and aged rats. Thus, it was suggested that curcuminoids may act as a putative drug candidate for the prevention of deleterious effects of ageing and age associated neurodegenerative disorders through amelioration of aberrant mitochondrial functioning. PMID:24048922
Rastogi, Manisha; Ojha, Rudra P; Sagar, Chandrasekhar; Agrawal, Aruna; Dubey, Govind P
Severity of Alcohol-Induced Painful Peripheral Neuropathy in Female Rats: Role of Estrogen and Protein Kinase (A and C?)
Small-fiber painful peripheral neuropathy, a complication of chronic ethanol ingestion, is more severe in women. In the present study, we have replicated this clinical finding in the rat and evaluated for a role of estrogen and second messenger signaling pathways. The alcohol diet (6.5% ethanol v:v in Lieber-DeCarli formula) induced hyperalgesia with more rapid onset and severity in females. Following ovariectomy, alcohol failed to induce hyperalgesia in female rats, well past its time to onset in gonad intact males and females. Estrogen replacement reinstated alcohol neuropathy in the female rat. The protein kinase A (PKA) inhibitor (WIPTIDE) only attenuated alcohol-induced hyperalgesia in female rats. Inhibitors of protein kinase C? (PKC?-I) and ERK1/2 (PD98059 and U0126) attenuated hyperalgesia in males and females, however the degree of attenuation produced by PKC?-I was much greater in females. In conclusion, estrogen plays an important role in the expression of pain associated with alcohol neuropathy in the female rat. In contrast to inflammatory hyperalgesia, in which only the contribution of PKC? signaling is sexually dimorphic, in alcohol neuropathy PKA as well as PKC? signaling is highly sexually dimorphic.
Dina, Olayinka A.; Gear, Robert W.; Messing, Robert O.; Levine, Jon D.
Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats
Phytoestrogens are plant compounds that structurally mimic the endogenous estrogen 17{beta}-estradiol (E{sub 2}). Despite intense investigation, the net effect of phytoestrogen exposure on the breast remains unclear. The objective of the current study was to examine the effects of quercetin on E{sub 2}-induced breast cancer in vivo. Female ACI rats were given quercetin (2.5 g/kg food) for 8 months. Animals were monitored weekly for palpable tumors, and at the end of the experiment, rats were euthanized, breast tumor and different tissues excised so that they could be examined for histopathologic changes, estrogen metabolic activity and oxidant stress. Quercetin alone did not induce mammary tumors in female ACI rats. However, in rats implanted with E{sub 2} pellets, co-exposure to quercetin did not protect rats from E{sub 2}-induced breast tumor development with 100% of the animals developing breast tumors within 8 months of treatment. No changes in serum quercetin levels were observed in quercetin and quercetin + E{sub 2}-treated groups at the end of the experiment. Tumor latency was significantly decreased among rats from the quercetin + E{sub 2} group relative to those in the E{sub 2} group. Catechol-O-methyltransferase (COMT) activity was significantly downregulated in quercetin-exposed mammary tissue. Analysis of 8-isoprostane F{sub 2{alpha}} (8-iso-PGF{sub 2{alpha}}) levels as a marker of oxidant stress showed that quercetin did not decrease E{sub 2}-induced oxidant stress. These results indicate that quercetin (2.5 g/kg food) does not confer protection against breast cancer, does not inhibit E{sub 2}-induced oxidant stress and may exacerbate breast carcinogenesis in E{sub 2}-treated ACI rats. Inhibition of COMT activity by quercetin may expose breast cells chronically to E{sub 2} and catechol estrogens. This would permit longer exposure times to the carcinogenic metabolites of E{sub 2} and chronic exposure to oxidant stress as a result of metabolic redox cycling to estrogen metabolites, and thus quercetin may exacerbate E{sub 2}-induced breast tumors in female ACI rats.
Singh, Bhupendra [Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108 (United States); Mense, Sarah M. [Department of Environmental Health Sciences, Columbia University, New York, NY 10032 (United States); Bhat, Nimee K. [Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108 (United States); Putty, Sandeep; Guthiel, William A. [Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108 (United States); Remotti, Fabrizio [Department of Pathology, Columbia University, New York, NY 10032 (United States); Bhat, Hari K., E-mail: firstname.lastname@example.com [Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108 (United States)
Fluence-to-absorbed-dose conversion coefficients for neutron beams from 0.001 eV to 100 GeV calculated for a set of pregnant female and fetus models
NASA Astrophysics Data System (ADS)
Protection of fetuses against external neutron exposure is an important task. This paper reports a set of absorbed dose conversion coefficients for fetal and maternal organs for external neutron beams using the RPI-P pregnant female models and the MCNPX code. The newly developed pregnant female models represent an adult female with a fetus including its brain and skeleton at the end of each trimester. The organ masses were adjusted to match the reference values within 1%. For the 3 mm cubic voxel size, the models consist of 10-15 million voxels for 35 organs. External monoenergetic neutron beams of six standard configurations (AP, PA, LLAT, RLAT, ROT and ISO) and source energies 0.001 eV-100 GeV were considered. The results are compared with previous data that are based on simplified anatomical models. The differences in dose depend on source geometry, energy and gestation periods: from 20% up to 140% for the whole fetus, and up to 100% for the fetal brain. Anatomical differences are primarily responsible for the discrepancies in the organ doses. For the first time, the dependence of mother organ doses upon anatomical changes during pregnancy was studied. A maximum of 220% increase in dose was observed for the placenta in the nine months model compared to three months, whereas dose to the pancreas, small and large intestines decreases by 60% for the AP source for the same models. Tabulated dose conversion coefficients for the fetus and 27 maternal organs are provided.
Taranenko, Valery; Xu, X. George
Pelvic Organ Distribution of Mesenchymal Stem Cells Injected Intravenously after Simulated Childbirth Injury in Female Rats
The local route of stem cell administration utilized presently in clinical trials for stress incontinence may not take full advantage of the capabilities of these cells. The goal of this study was to evaluate if intravenously injected mesenchymal stem cells (MSCs) home to pelvic organs after simulated childbirth injury in a rat model. Female rats underwent either vaginal distension (VD) or sham VD. All rats received 2 million GFP-labeled MSCs intravenously 1 hour after injury. Four or 10 days later pelvic organs and muscles were imaged for visualization of GFP-positive cells. Significantly more MSCs home to the urethra, vagina, rectum, and levator ani muscle 4 days after VD than after sham VD. MSCs were present 10 days after injection but GFP intensity had decreased. This study provides basic science evidence that intravenous administration of MSCs could provide an effective route for cell-based therapy to facilitate repair after injury and treat stress incontinence.
Cruz, Michelle; Dissaranan, Charuspong; Cotleur, Anne; Kiedrowski, Matthew; Penn, Marc; Damaser, Margot
Prenatal Bystander Stress Alters Brain, Behavior, and the Epigenome of Developing Rat Offspring
The prenatal environment, including prenatal stress, has been extensively studied in laboratory animals and humans. However, studies of the prenatal environment usually directly stress pregnant females, but stress may come 'indirectly', through stress to a cage-mate. The current study used indirect prenatal bystander stress and investigated the effects on the gross morphology, pre-weaning behavior, and epigenome of rat offspring. Pregnant
Richelle Mychasiuk; Nichole Schmold; Slava Ilnytskyy; Olga Kovalchuk; Bryan Kolb; Robbin Gibb
Reproductive Experience and the Response of Female Sprague-Dawley Rats to Fear and Stress
The present work examines the relationship between reproductive experience (comprising breeding, parturition, and lactation) and the behavioral and hormonal processes of fear and stress in the female laboratory rat. Previous research has indicated that reproductive experience functions to decrease the female's stress response in potentially harmful environments, thereby providing her with numerous survival benefits, including decreased fearfulness, increased aggression, and refined hunting skills. This study was designed to determine how nulliparous (no reproductive experience), primiparous (1 reproductive experience) and multiparous (at least 2 reproductive experiences) rats respond to a Pavlovian paradigm of learned fear, involving the pairing of a neutral stimulus (conditioned stimulus) with an aversive stimulus (unconditioned stimulus). We report evidence that reproductive experience is linked with fear-response and anxiety-like behaviors. Our findings indicate that reproductive experience has an additive effect: primiparous mothers showed a different response to the paradigm of conditioned fear not only compared with those of nulliparous rats as well as multiparous mothers. Assessing the complex interconnections among the behavioral and physiologic measures recorded in this study, multidimensional scaling confirmed a clear separation among the 3 groups of rats in terms of the behavioral and physiologic responses to the experimental paradigm, supporting the conclusion that reproductive experience influences the maternal mind.
Rima, Brandi N; Bardi, Massimo; Friedenberg, Julia M; Christon, Lillian M; Karelina, Kate E; Lambert, Kelly G; Kinsley, Craig H
Reproductive suppression in female Damaraland mole-rats Cryptomys damarensis: dominant control or self-restraint?
Colonies of Damaraland mole-rats Cryptomys damarensis exhibit a high reproductive skew. Typically one female breeds and the others are anovulatory. Two models, the dominant control model (DCM) and the self-restraint model (SRM), have been proposed to account for this reproductive suppression. The DCM proposes that suppression is under the control of the dominant breeder and is imposed by mechanisms such as aggression, pheromones and interference with copulation, whereas the SRM does not involve aggression directed towards non-breeders and may function in order to minimize inbreeding. We investigated potential proximate mechanisms involved in the suppression of females in a series of experiments. Socially induced stress through aggression did not appear to be responsible for anovulation. Nor did breeders actively interfere with subordinate copulation. Females were physiologically suppressed when housed in intact colonies. However, as predicted by the DCM, they did not become reproductively active when removed from the presence of breeders. We found no evidence that pheromonal cues block ovulation. We suggest that the SRM is the basic model found in the Damaraland mole-rat and that self-restraint functions in order to minimize inbreeding by restricting reproduction until an unrelated male is present. This would explain the rapid onset of reproductive activation in females when paired with an unrelated male, as demonstrated in this study. PMID:11370962
Clarke, F M; Miethe, G H; Bennett, N C
Effect of Symplocos racemosa Roxb. on gonadotropin release in immature female rats and ovarian histology.
In the present study we are reporting in vivo effect of aqueous extracts of Symplocos racemosa Roxb. (Fam. Symplocaceae) on serum FSH and LH levels in immature female Sprague-Dawley rats under basal conditions. Symplocos racemosa is used in Indian System of Medicine (ISM) for various female disorders. Aqueous extract on oral administration significantly stimulated serum FSH level (P < 0.016) along with the rise in serum LH level (P < 0.001). Moreover, histopathological studies revealed enhanced folliculogenesis, presence of mature follicles and detached oocytes, which are result of increased FSH and LH levels. Further, an increase in the ovary weight of treated animals was found due to observed FSH surge. These results are in concordance with the traditional use of the drug for female disorders. PMID:15261983
Bhutani, Kamlesh Kumar; Jadhav, Atul N; Kalia, Vandana
The influence of sleep deprivation and obesity on DNA damage in female Zucker rats
OBJECTIVE: The aim of this study was to evaluate overall genetic damage induced by total sleep deprivation in obese, female Zucker rats of differing ages. METHOD: Lean and obese Zucker rats at 3, 6, and 15 months old were randomly distributed into two groups for each age group: home-cage control and sleep-deprived (N?=?5/group). The sleep-deprived groups were deprived sleep by gentle handling for 6 hours, whereas the home-cage control group was allowed to remain undisturbed in their home-cage. At the end of the sleep deprivation period, or after an equivalent amount of time for the home-cage control groups, the rats were brought to an adjacent room and decapitated. The blood, brain, and liver tissue were collected and stored individually to evaluate DNA damage. RESULTS: Significant genetic damage was observed only in 15-month-old rats. Genetic damage was present in the liver cells from sleep-deprived obese rats compared with lean rats in the same condition. Sleep deprivation was associated with genetic damage in brain cells regardless of obesity status. DNA damage was observed in the peripheral blood cells regardless of sleep condition or obesity status. CONCLUSION: Taken together, these results suggest that obesity was associated with genetic damage in liver cells, whereas sleep deprivation was associated with DNA damage in brain cells. These results also indicate that there is no synergistic effect of these noxious conditions on the overall level of genetic damage. In addition, the level of DNA damage was significantly higher in 15-month-old rats compared to younger rats.
Tenorio, Neuli M.; Ribeiro, Daniel A.; Alvarenga, Tathiana A.; Fracalossi, Ana Carolina C.; Carlin, Viviane; Hirotsu, Camila; Tufik, Sergio; Andersen, Monica L.
Time-specific effects of perinatal glucocorticoid treatment on anterior pituitary morphology, annexin 1 expression and adrenocorticotrophic hormone secretion in the adult female rat.
Perinatal glucocorticoid (GC) treatment is increasingly associated with long-term disturbances in hypothalamo-pituitary-adrenocortical function. In the male rat, such treatment induces profound molecular, morphological and functional changes in the anterior pituitary gland at adulthood. To determine whether these effects are sex-specific, we have examined the effects of perinatal dexamethasone treatment on the female pituitary gland, focusing on (i) the integrity of the annexin 1 (ANXA1) dependent regulatory effects of GCs on adrenocorticotrophic hormone (ACTH) release and (ii) corticotroph and folliculo-stellate (FS) cell morphology. Dexamethasone was given to pregnant (gestational days 16-19) or lactating (days 1-7 post partum) rats via the drinking water (1 microg/ml); controls received normal drinking water. Pituitary tissue from the female offspring was examined ex vivo at adulthood (60-90 days). Both treatment regimes reduced the intracellular and cell surface ANXA1 expression, as determined by western blot analysis and quantitative immunogold electron microscopic histochemistry. In addition, they compromised the ability of dexamethasone to suppress the evoked release of ACTH from the excised tissue in vitro, a process which requires the translocation of ANXA1 from the cytoplasm to the cell surface of FS cells. Although neither treatment regime affected the number of FS cells or corticotrophs, both altered the subcellular morphology of these cells. Thus, prenatal dexamethasone treatment increased while neonatal treatment decreased FS cell size and cytoplasmic area. By contrast, corticotroph size was unaffected by either treatment, as also was the size of the secretory granules. Corticotroph granule density and margination were, however, increased markedly by the prenatal treatment, while the neonatal treatment had no effect on granule density but decreased granule margination. Thus, perinatal dexamethasone treatment exerts long-term effects on the female pituitary gland, altering gene expression, cell morphology and the ANXA1-dependent GC regulation of ACTH secretion. The changes are similar but not identical to those reported in the male. PMID:17076770
John, C D; Theogaraj, E; Christian, H C; Morris, J F; Smith, S F; Buckingham, J C
Hepatic Protection by Noni Fruit Juice Against CCl 4 Induced Chronic Liver Damage in Female SD Rats
Morinda citrifolia L. (noni) has been used throughout the Pacific, Southeast Asia, Central America, and the Caribbean for a variety of health\\u000a conditions, including heart and liver ailments. In this study, we examined the hepatoprotective effects of TAHITIAN NONI®\\u000a Juice (TNJ) against CCl4-induced chronic liver damage in female Sprague Dawley (SD) rats. Twelve female SD rats were divided into control,
Mian-Ying Wang; Gary Anderson; Diane Nowicki; Jarakae Jensen
Antioxidant defense system in lung of male and female rats: Interactions with alcohol, copper, and type of dietary carbohydrate
Male and female rats were used to investigate the effects of type of dietary carbohydrate (CHO), copper, and ethanol consumption on lung antioxidant enzyme activities and levels of phosphorylated compounds in whole blood. Copper-deficient female rats exhibited a greater degree of copper deficiency than males, as assessed by hepatic copper concentration and hepatic copper superoxide dismutase (CuSOD) activity. However, copper-deficient
Meira Fields; Charles G. Lewis; Mark D. Lure
Effects of Stimulation and Blockade of D2 Receptor on Depression-Like Behavior in Ovariectomized Female Rats
The aim of the present study was to explore the hedonic effects of D2 receptor agonist, quinpirole and D2 receptor antagonist, and sulpiride alone or in combination with a low dose of 17?-E2-estradiol (17?-E2) in the adult ovariectomized female rats (OVX). OVX rats of Wistar strain were used in all experiments. Two weeks after surgery rats were chronically treated with vehicle, a low dose of 17?-E2 (5.0??g/rat), quinpirole (0.1?mg/kg), sulpiride (10.0?mg/kg), quinpirole plus 17?-E2, or sulpiride plus 17?-E2 for 14 days before the forced swimming test. We found that sulpiride significantly decreased immobility time in the OVX females. A combination of sulpiride with a low dose of 17?-E2 induced more profound decrease of immobility time in the OVX rats compared to the rats treated with sulpiride alone. On the contrary, quinpirole failed to modify depression-like behavior in the OVX rats. In addition, quinpirole significantly blocked the antidepressant-like effect of 17?-E2 in OVX rats. Thus, the D2 receptor antagonist sulpiride alone or in combination with a low dose of 17?-E2 exerted antidepressant-like effect in OVX female rats, while the D2 receptor agonist quinpirole produced depressant-like profile on OVX rats.
Fedotova, Julia
Acute predator stress impairs the consolidation and retrieval of hippocampus-dependent memory in male and female rats
We have studied the effects of an acute predator stress experience on spatial learning and memory in adult male and female Sprague-Dawley rats. All rats were trained to learn the location of a hidden escape platform in the radial-arm water maze (RAWM), a hippocampus-dependent spatial memory task. In the control (non-stress) condition, female rats were superior to the males in the accuracy and consistency of their spatial memory performance tested over multiple days of training. In the stress condition, rats were exposed to the cat for 30 min immediately before or after learning, or before the 24-h memory test. Predator stress dramatically increased corticosterone levels in males and females, with females exhibiting greater baseline and stress-evoked responses than males. Despite these sex differences in the overall magnitudes of corticosterone levels, there were significant sex-independent correlations involving basal and stress-evoked corticosterone levels, and memory performance. Most importantly, predator stress impaired short-term memory, as well as processes involved in memory consolidation and retrieval, in male and female rats. Overall, we have found that an intense, ethologically relevant stressor produced a largely equivalent impairment of memory in male and female rats, and sex-independent corticosterone-memory correlations. These findings may provide insight into commonalities in how traumatic stress affects the brain and memory in men and women.
Park, Collin R.; Zoladz, Phillip R.; Conrad, Cheryl D.; Fleshner, Monika; Diamond, David M.
Blood risk factor metabolites associated with heart disease and myocardial fatty acids in copper-deficient male and female rats
Intact and castrated males and intact and ovariectomized female rats were fed a copper-deficient diet in order to establish whether the protection provided in females against cardiovascular pathology and mortality is due to endogenous sex hormones, and different levels of blood lipids and/or myocardial fatty acids. Seventy-three male and female rats were assigned to a copper-deficient diet (0.6 {mu}g of copper/g diet) containing 62% fructose for 8 weeks. Twelve of the male rats underwent castration and 12 of the females were ovariectomized. All animals exhibited high levels of plasma cholesterol, triglycerides, and uric acid, which were neither affected by the sex of the rat nor by the surgical treatment. The composition of fatty acids of the myocardium was similar in males and females. Except for those animals that were sacrificed by us, all other male rats died of heart pathology. In contrast, none of the female rats exhibited heart pathology and none died of the deficiency. It is suggested that heart pathology and mortality in copper deficiency are sex related and not due to high levels of plasma cholesterol, triglycerides, and uric acid or to differences in myocardial fatty acid composition.
Fields, M.; Lewis, C.; Beal, T. (Georgetown Univ. Medical School, WA (USA)); Berlin, E.; Kliman, P.G.; Peters, R.C. (Department of Agriculture, Beltsville, MD (USA))
Effects of Salsalate Therapy on Recovery From Vascular Injury in Female Zucker Fatty Rats
OBJECTIVE Salsalate is a dimeric form of salicylic acid that has been shown to have anti-inflammatory activity and to reduce glucose levels, insulin resistance, and cytokine expression. However, the effect of salsalate on vascular injury has not been determined. The objective of this study is to investigate the effect of salsalate on vascular injury and repair in a rat model of carotid artery balloon catheter injury. RESEARCH DESIGN AND METHODS Salsalate treatment was started in female Zucker fatty rats (insulin resistant) 1 week before carotid artery balloon catheter injury and continued for 21 days, at which time the animals were killed and studied. RESULTS Treatment with salsalate significantly decreased the intima-to-media ratio and upregulated the expression of aortic endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) (ser 1177), and manganese superoxide dismutase (MnSOD) and reduced serum interleukin (IL)-6 with concomitant downregulation of nuclear factor (NF) ?B subunit p65 and vascular endothelial growth factor (VEGF) expression in the balloon-injured carotid artery of female Zucker fatty rats. CONCLUSIONS The present study shows that salsalate treatment decreases vascular damage caused by balloon catheter injury in female Zucker fatty rats. The beneficial effect of salsalate on vascular injury was associated with upregulation of eNOS, p-eNOS, and MnSOD, which reduce oxidative stress and have anti-inflammatory properties, as evidenced by reduction in serum IL-6 and the downregulation of VEGF and NF?B, which promote inflammation without changing glucose levels. These results suggest that salsalate may be useful in reducing vascular injury and restenosis following interventional revascularization procedures.
Murthy, Subramanyam N.; Desouza, Cyrus V.; Bost, Neal W.; Hilaire, Rose-Claire St.; Casey, David B.; Badejo, Adeleke M.; Dhaliwal, Jasdeep S.; McGee, Jennifer; McNamara, Dennis B.; Kadowitz, Philip J.; Fonseca, Vivian A.
Impaired spatial navigation in adult female but not adult male rats exposed to alcohol during the brain growth spurt.
Two groups of male and female rats were given the same dose of alcohol using an artificial rearing procedure on postnatal days 4-10. One group received the alcohol in a condensed manner each day which caused cyclic blood alcohol concentrations (BACs) with high peaks. A second group received the alcohol in a uniform manner over each day which resulted in moderate, stable BACs. Two control groups consisted of male and female rats artificially reared but not exposed to alcohol and rats reared normally by dams. All rats were raised to 90 days of age and then tested for spatial navigation ability in the Morris water maze, which involved locating a hidden underwater platform using distal extramaze cues. Neither the alcohol treatments nor the artificial rearing had any effects on performance of adult male rats relative to suckle controls in this task. In contrast, the condensed alcohol exposure but not the uniform alcohol exposure resulted in detrimental performance in the Morris water maze by adult female rats. When the ability to locate and escape onto a visible platform was examined, there were no differences between the female groups given condensed alcohol exposure or artificially reared on milk solution alone. Thus, exposure to high BACs during the brain growth spurt has a lasting and selective detrimental effect on spatial navigation learning in adult female but not adult male rats. PMID:3358862
Kelly, S J; Goodlett, C R; Hulsether, S A; West, J R
Chronically stressed female rats show increased anxiety but no behavioral alterations in object recognition or placement memory: a preliminary examination.
Stress, depending on intensity and duration, elicits adaptive or maladaptive physiological effects. Increasing evidence shows those patterns of advantageous versus deleterious physiologic stress effects also exist for some brain functions, including learning and memory. For example, short stress enhances, while chronic stress impairs, performance on numerous cognitive tasks in male rats. In contrast, performance of female rats is enhanced, or not altered, following both short-term and long-term stress exposure on the same behavioral tasks. The current study was designed to better characterize the behavioral effects of sustained chronic restraint stress in female rats. Female Sprague Dawley rats were assigned to a stress (restraint, 6 h/day, 35 days) or control (no stress) condition, weighed weekly, and then tested on open field (OF), object recognition (OR) and object placement (OP) tasks. Stressed females gained less weight during stress than controls. On the OF, there were no group differences in locomotor activity, but stressed females made fewer inner visits than controls, indicating increased anxiety. Both groups successfully performed the OP and OR tasks across all inter-trial delays, indicating intact non-spatial and spatial memory in both control and stress females. The current results provide preliminary evidence that the commonly used chronic restraint stress model may not be an efficient stressor to female rats. PMID:22168672
Bowman, R E; Kelly, R
Modulation in reproductive tissue redox profile in sexually receptive female rats after short-term exposure to male chemical cues.
It is well known that antioxidants play an important role in sperm fertility, but there is no data on the literature regarding the effect of male chemical cues in the antioxidant defenses of the female reproductive tract. Here, we evaluated oxidative parameters in ovaries and uterus of virgin female rats isolated from contact to males and exposed only to male-soiled bedding (MSB). Four-month-old Wistar (regular 4-day cyclic) virgin female rats were utilized from proestrus to estrus phase of the reproductive cycle for experimental exposure. In an isolated room, female rats were exposed for 90 min to MSB. For biochemical assays, female rats were killed by decapitation at 30, 90, 180, and 240 min after the end of exposure, and the ovaries and uterus were removed for further analysis. Antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase), the nonenzymatic antioxidant potential (total radical-trapping antioxidant parameter), and the oxidative damage parameters (thiobarbituric acid-reactive species and carbonyl content) were analyzed. We observed an increase in the nonenzymatic antioxidant potential and diminished free radical oxidative damage in uterine tissue, 30 and 90 min after exposure. Furthermore, in ovaries, enzymatic defenses were modulated distinctly along the 240 min after exposure. MSB exposure modulates the antioxidant profile in ovaries and uterus of receptive female rats. It is possible that the modifications in the oxidative profile of the female genital tract may have important implications in the process of fertilization. PMID:19188278
Behr, Guilherme Antônio; da Motta, Leonardo Lisbôa; de Oliveira, Marcos Roberto; Oliveira, Max William Soares; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca
Consummatory, anxiety-related and metabolic adaptations in female rats with alternating access to preferred food
Summary Avoidance of and relapse to palatable foods is a qualitative aspect of dieting, a putative risk factor for eating disorders or obesity. The present studies tested the hypotheses that rats with alternating access to highly preferred foods would show: (1) hypophagia, a function of the relative hedonic value of the underaccepted diet, (2) increased anxiety-like behavior and psychomotor ar006Fusal when preferred diet was unavailable, (3) obesity-like changes, and (4) stable individual differences in diet-switch-induced hypophagia. Preferences among three high-carbohydrate diets were determined in female Wistar rats (n = 16). Adolescent rats (n = 162) received the following weekly diet schedules: (1) continuous regular chow (7 days/week), (2) chow (5 days/week) followed by a more preferred diet (2 days/week), or (3) chow (5 days/week) followed by a less preferred chow (2 days/week). Some animals were yoke-restricted (75% calories) when provided chow to increase its rewarding properties. Diurnal locomotor activity was measured in a familiar environment, and anxiety-like behavior was assessed in the elevated plus-maze and defensive withdrawal tests. Rats withdrawn from the preferred diet showed hypophagia, anxiogenic-like behavior, increased locomotion, and weight loss. Chow hypophagia was progressive, individual-specific in magnitude, (partly) non-homeostatic in nature, and blunted by previous chow restriction. Despite eating less, rats cycled with the preferred diet became heavier, fatter, and diurnally less active, with greater feed efficiency and proinflammatory
Cottone, Pietro; Sabino, Valentina; Steardo, Luca; Zorrilla, Eric P.
Marginal Growth Increase, Altered Bone Quality and Polycystic Ovaries in Female Prepubertal Rats after Treatment with the Aromatase Inhibitor Exemestane
Background: Aromatase inhibition has been proposed as a potential approach for growth enhancement in children with short stature, but detailed animal studies are lacking. Aim: To assess the effect and potential adverse effects of aromatase inhibition on growth in female rats. Methods: Prepubertal Wistar rats received intramuscular injections with placebo or the aromatase inhibitor exemestane at a dose of 10,
Sandy A. van Gool; Jan M. Wit; Tineke De Schutter; Nora De Clerck; Andreď A. Postnov; Sandra Kremer Hovinga; Jaap van Doorn; Sergio J. Veiga; Luis Miguel Garcia-Segura; Marcel Karperien
Chlamydia trachomatis Infection in the Female Reproductive Tract of the Rat: Influence of Progesterone on Infectivity and Immune Response
As the most common cause of sexually transmitted disease in women, chlamydial infections can lead to pelvic inflammatory disease, infertility, and ectopic pregnancy. To better understand the role played by sex hormones in modulating the immune response of the genital tract to microbial infections, we have developed a rat model to study Chlamydia trachomatis infection. Inbred female Lewis rats were
Developmental Neurobehavioral Effects on JP-8 Jet Fuel on Pups from Female Sprague-Dawley Rats Exposed by Oral Gavage.
National Technical Information Service (NTIS)
U.S. military personnel are exposed frequently to the jet fuel JP-8 since it became the standardized military fuel. Limited reproductive studies in rats have been conducted with JP-8. Female rats were dosed with 0, 325. 750 or 1500 mg/kg-day neat JP-8 by ...
D. R. Mattie J. R. Cooper T. R. Sterner B. D. Schimmel M. Y. Bekkedal