Melatonin ameliorates PM2.5‐induced spermatogenesis disorder by preserving H3K9 methylation and SIRT3

Abstract There was a link between exposure to PM2.5 and male infertility. Melatonin has beneficial effects on the male reproductive processes. How PM2.5 caused spermatogenesis disturbance and whether melatonin could prevent PM2.5‐induced reproductive toxicity have remained unclear. The results showed that PM2.5 could inhibit the Nrf2‐mediated antioxidant pathway and distinctly increase the cell apoptosis in testes. Moreover, PM2.5 also perturbed the process of meiosis by modulating meiosis‐associated proteins such as γ‐H2AX and Stra8. Mechanistically, PM2.5 inhibited G9a‐dependent H3K9 methylation and SIRT3‐mediated p53 deacetylation, which consistent with decreased sperm count and motility rate in ApoE −/− mice. Further investigation revealed melatonin effectively alleviated PM2.5‐induced meiosis inhibition by preserving H3K9 methylation. Melatonin also alleviated PM2.5‐induced apoptosis by regulating SIRT3‐mediated p53 deacetylation. Overall, our study revealed PM2.5 resulted in spermatogenesis disorder by perturbing meiosis via G9a‐dependent H3K9 di‐methylation and causing cell apoptosis via SIRT3/p53 deacetylation pathway and provided promising insights into the protective role of melatonin in air pollution associated with male infertility.