Melatonin ameliorates Bisphenol S induced testicular damages by modulating Nrf-2/HO-1 and SIRT-1/FOXO-1 expressions.

Abstract

BPS has detrimental effects on human reproductive health and emerged as an environmental contaminant for global health concern. This study deals with the adverse impact of BPS exposure on testicular oxidative stress, inflammation and apoptosis in adult male golden hamster, Mesocricetus auratus and its amelioration by melatonin. BPS (75 mg/kg BW/day) exposure caused testicular impairment as evident by histological degenerative changes, declined sperm quality (viability and motility), serum levels of testosterone and melatonin with a concomitant decrease in testicular androgen receptor (AR) and melatonin receptor (MT1) expression. The BPS exposure caused marked increase in testicular oxidative load, inflammation (NF-kB/COX-2) and apoptosis (caspase-3). Melatonin (10 mg/kg BW/alternate day) pretreatment to BPS exposed hamsters resumed normal testicular histoarchitecture, sperm quality and decreased testicular oxidative load as evident by enhanced antioxidant enzymes (SOD and catalase) activities and decreased lipid peroxidation (LPO) level. Further, melatonin also stimulated the testicular antioxidant proteins Nrf-2/HO-1, SIRT-1/FOXO-1 and reduced inflammatory proteins NF-kB/COX-2 expression to counteract BPS induced testicular damages. Melatonin administration to the BPS treated hamsters resulted in increased testicular cell proliferation (PCNA), survival (Bcl-2), gap junction (connexin-43) and decreased apoptosis (caspase-3). In conclusion, our study documented the detrimental effects of BPS on testes that compromises male fertility. Further, melatonin was found as a potent molecule that rescued the BPS induced testicular damages in male golden hamster Mesocricetus auratus.