Melatonin attenuates Δ
The use of Cannabis sativa (CS) has been widely demonstrated to have detrimental effect on male reproductive functions. Despite the well-known existence of endocannabinoid and melatonergic systems in semen, the physiological significance of their interaction is not understood. We recently showed that melatonin exacerbates the CS-induced gonadotoxicity in-vivo. To overcome the limitations associated with our in-vivo studies and further understand the role of cannabinoid-melatonin relationship in sperm functions, this study investigated the in-vitro effect of tetrahydrocannabinol (THC) andor melatonin on motility and kinematics of capacitating rat sperms. Rat semen was randomly divided into 9 treatment groups (n 5) as follow Groups 1-4 were treated with placebo, SR141716 (1 mM), AM-630 (1 mM), and THC (1 mM) respectively. Groups 5-7 were pre-treated with SR141716, AM-630, and their combination respectively, followed by THC after 5 min. Group 8 was treated with melatonin (5 mM), while group 9 was treated with THC and melatonin. THC-induced reduction in sperm motility and kinematics were partly inhibited by cannabinoid receptor (CB) 1 or 2 blockade, but abolished by blockade of both CBs. Interestingly, melatonin increased the progressive motility and kinematics of rat sperms when administered alone and also attenuated THC-induced reduction in progressive motility (by 42%) and kinematics. The hyper-activated motility of capacitated sperms treated with cannabinoids andor melatonin is determined largely by sperm velocities, amplitude of lateral head and beatcross frequency but less by velocity ratios. Conclusively, the spermatotoxic effect of THC is mediated by CBs 1 and 2 and is ameliorated by melatonin in-vitro.