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Early life exposure to soy isoflavones programs growth and reproductive organ development

Exposure to soy isoflavones (ISO), with potential estrogen‐like activity, for the first 5 days of life results in higher weight gain and reduced fertility in female adult mice. This study determined if longer exposure to ISO results in greater weight gain, and if the histological changes in reproductive tissues may explain reduced fertility with ISO exposure. ISO, 7 mg/kg body weight, were administered to female CD‐1 mice (n=8–13/group) by subcutaneous injection once daily from postnatal day (PND) 1–10 or PND 1–21. Body weight was measured weekly from 4–8 weeks. Mice were killed at age 4 months and reproductive organ weight and histology determined. From age 4 through 8 weeks, ISO groups were heavier (p≤0.05) than controls and the 21‐day ISO‐treated mice were also heavier (p≤0.05) than mice exposed to ISO for 10 days. Absent or lower numbers of corpus lutea (p≤0.05), a marker of abnormal ovary development, were observed in both ISO groups and may explain absent ovulation and reduced fertility observed in this group. ISO exposure resulted in uterine endometrial hyperplasia with atypia, polyps and adenomyosis (p≤0.05), implying a risk of tumor development. Despite marked histological changes in uterus and ovaries, tissue weight was similar among groups. Longer exposure to ISO during early life causes greater weight gain in adulthood and histological changes in the uterus and ovary that may compromise fertility in this model.