Hexavalent chromium (Cr (VI)) is a widely used metal and has been shown to cause male reproductive abnormalities. However, the underlying mechanisms for the Cr (VI)-induced reproductive toxicity remain incompletely understood. In this study, we investigated the spermatogonial damage caused by Cr (VI) as well as the protective effect of melatonin against Cr (VI)-triggered toxicity. We observed that Cr (VI) caused spermatogonial damage in a time- and dose-dependent manner. Results further showed that melatonin could protect spermatogonia from Cr (VI)-triggered damage via elimination of reactive oxygen species (ROS) as well as via suppression of ATM-p53 phosphorylation and the mitogen-activated protein kinase (MAPK) pathway. Prior administration of melatonin also prevented the Cr (VI)-caused enrichment of H3K9me3 in the Mad1, Mad2 and Bcl2 gene promoter regions, precluding the G2/M arrest and apoptosis in spermatogonia. Taken together, this study demonstrates that melatonin can effectively protect spermatogonia against the damage and against the histone modification changes induced by Cr (VI). This, along with the uncovered molecular mechanism, provide important implications for male infertility induced by environmental pollution.
Keywords: Hexavalent chromium; Histone modification; Melatonin; Mitogen-activated protein kinase; Reactive oxygen species; Spermatogonia.
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