Melatonin alleviates oxidative damage in mouse spermatogenesis and sperm quality parameters induced by exposure to Bisphenol A

Bisphenol A (BPA) exposure is known to cause damage to male fertility. Conversely, melatonin (MLT) has been shown to offer protection against reproductive damage by acting as an antioxidant. Exploration into the molecular mechanisms behind how MLT alleviates BPA-induced male fertility damage remains unclear. In this study, adult male mice were divided into four groups of control, BPA exposure (intragastrically, 50 mg/kg/day), MLT treatment (intraperitoneal injection, 10 mg/kg/day) and combined BPA+MLT treatment group for comparative analysis after five weeks of treatment. BPA exposure led to male mice subfertility characterized by poor sperm quality of decreased sperm counts and motility, and reduced pregnancy rate of female mice in in vivo and blastocyst formation in vitro experiments. In BPA exposed mice, germ cell proliferation was impaired, showing a decrease in PCNA expression. BPA exposure also induced a decrease in the expression of antioxidant molecules Cat, Prdx6, and Sod1, and up-regulated BAX expression. These expression changes resulted in increased germ cell apoptosis detected by TUNEL experiments. MLT treatment significantly maintained male mice sperm quality and fertility adversely affected by BPA through modulating the abovementioned responses. Sperm proteomics identified 118 BPA-regulated proteins whose expression was changed by MLT treatment, including 37 down-regulated proteins related to proteolysis activity, the up-regulated proteins were mainly involved in lipid metabolism. Conclusively, BPA exposure impaired male fertility by negatively affecting germ cell proliferation and sperm quality. MLT treatment could alleviate the side effects of BPA by regulating antioxidant molecules, inhibiting germ cell apoptosis, and maintaining male fertility. This study will provide more information for further exploration into the molecular mechanisms of BPA and MLT in male reproduction.