Melatonin Prevents the Adverse Effects of Leptin on Histone-to-Protamine Transition during Spermatogenesis in Rats

Abstract

The aim of this study was to examine the effect of melatonin on leptin induced changes in transition of histone to protamine in adult rats during spermatogenesis. Twelve-week old Sprague-Dawley rats were randomized into control, leptin, leptin-melatonin-10, leptin-melatonin-20 and melatonin-10 treated groups with 6 rats per group. Leptin-treated groups received intra-peritoneal injections (i.p.) of leptin daily for 42 days (60 µg/kg body weight). Rats in the leptin and melatonin treated groups were given either 10 or 20 mg of melatonin/day/kg body weight in drinking water. Melatonin-10 treated group received only 10 mg of melatonin/day/kg body weight in drinking water for 42 days. Control rats received 0.1 ml of 0.9 % saline i.p. for 42 days. Upon completion of the treatment, sperm count, morphology and histone-to-protamine ratio estimation was performed. The expression of HAT, HDAC1, HDAC2, H2B, H2A, H1, PRM1, PRM2, TNP1 and TNP2 genes were analyzed using microarray analyses. Data were analyzed using ANOVA. Sperm count was significantly lower whereas the fraction of sperm with abnormal morphology, the ratio of histone-to-protamine transition and the level of HAT, HDAC1, HDAC2, H2B, H2A, H1, PRM1 were significantly higher in leptin treated rats. No significant differences were evident in these between controls and melatonin treated rats. It appears that exogenous leptin administration adversely affects histone-to-protamine transition, upregulates the genes involved in this replacement and these effects are prevented by concurrent administration of melatonin.