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This study investigated the role and mechanism of melatonin in alleviating Bisphenol A (BPA) -induced oxidative stress damage to the testes. Adult male mice received oral administration of 50 mg/kg BPA for 30 days along with subcutaneous injections of 20 mg/kg melatonin. Melatonin significantly increased the testis index and epididymis index in BPA-treated mice, promoted seminiferous tubule function, and increased sperm density and viability in the epididymal cauda. There were 262 common targets between the targets of melatonin and BPA-related testicular diseases, which were mainly involved in regulating cellular oxidative stress, mitochondrial quality control, mitochondrial function, steroid hormone synthesis, and cell apoptosis. In vivo, melatonin significantly increased MT1R (melatonin receptor 1A) expression in BPA-treated mouse testicular cells and the content of catalase, superoxide dismutase 2, and glutathione, while decreasing the level of malondialdehyde. Regarding mitochondria, melatonin significantly increased the protein expressions of OPA1, MFN1, MFN2, NRF1, and TFAM, while significantly reducing those of DRP1 and FIS1, restoring mitochondrial dynamic balance and biogenesis. Additionally, melatonin increased ATP production and mitochondrial respiratory chain complex I-V activity, thereby enhancing mitochondrial function. Finally, melatonin also increased the testosterone content, as well as the expression of steroidogenic acute regulatory protein and cytochrome P450 11A1 in testicular tissue, and reduced apoptosis of testicular cells. Conclusively, melatonin can alleviate testicular cell oxidative stress damage and mitochondrial dysfunction caused by BPA, increase testosterone synthesis and secretion, and reduce testicular cell apoptosis, thereby exerting an important protective effect on BPA-induced testicular damage.