Melatonin alleviates cisplatin-induced mice spermatogenesis defects

Cisplatin (CDDP) is a chemotherapeutic drug that is used to treat many different types of tumors. However, it also has significant adverse effects on male reproduction, which are partially mediated oxidative damage. Melatonin (MLT) is a promising antioxidant that can be used for reproductive protection. In this paper, we investigated the effect of CDDP on spermatogenesis, as well as MLT's potential role in reproductive protection. CDDP (5 mg/kg BW) significantly reduced male mice testosterone levels and decreased sperm vitality and progressive motility. Additionally, a lower percentage of stage VII and VIII seminiferous tubules were observed in CDDP-treated mice. MLT administration significantly alleviated CDDP-induced testicular damages, CDDP-induced lowered male fertility in vivo, and enhanced in vitro embryonic development of two cells and blastocysts. These changes may be due to CDDP-mediated spermatogenesis defects in germ cell and Leydig cell proliferation, which are reflected in abnormal PCNA, SYCP3, and CYP11A1 expression levels and can be improved by MLT. CDDP treatment significantly decreased the total antioxidant capacity (TAC), as well as SOD and GSH levels, and increased MDA levels in mice testis, leading to increased apoptosis of germ cells and increased BAX/BCL2 ratios in mice testis. MLT treatment may reduce germ cell apoptosis by reducing oxidative damage in mice testis. This study demonstrated that CDDP affects sperm fertility by altering germ cell and Leydig cell proliferation via increased oxidative damage and that MLT can attenuate these damages. Our work provides potential information for further research on the toxic effects of CDDP and the protective effects of MLT on male reproduction.