Family Planning Research Institute/Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Key Laboratory of Agro-product Safety and Quality, Institute of Quality Standards & Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, PR China..
J Inorg Biochem. 2019 Jan;190:67-74. doi: 10.1016/j.jinorgbio.2018.10.007. Epub 2018 Oct 18.
Methylmercury (MeHg) is a widespread environmental pollutant and causes a serious hazard to testicular development and spermatogenesis. However, molecular mechanisms underlying male reproductive toxicity induced by MeHg remain elusive. The objective of this study was to explore the effects of MeHg on autophagy induction in germ cells (GCs). In this study, we showed that orally administered MeHg 10 mg/kg per day for five consecutive days resulted in reduced sperm count and impaired sperm motility. Noteworthy, MeHg impaired the seminiferous tubule of rats and increased the apoptotic index of GCs of rats. Furthermore, the levels of the autophagy markers light chain 3-II (LC3-II) and beclin-1 were significantly increased following MeHg treatment, possibly via inhibiting the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (m-TOR) signaling pathway. In addition, these effects are concomitant with the overgeneration of reactive oxygen species (ROS) and the decreased expression of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). Interestingly, supplementation with MeHg induced oxidative DNA damage in testes of rats. Taken together, our data indicated that MeHg stimulates GC apoptosis through oxidative stress and autophagy, which may be the mechanism responsible for the regulation of testis function and differentiation following MeHg exposure.
甲基汞（MeHg）是一种广泛存在的环境污染物，对睾丸发育和精子发生造成严重危害。然而，甲基汞引起雄性生殖毒性的分子机制仍不清楚。本研究旨在探讨 MeHg 对生殖细胞（GCs）自噬诱导的影响。在这项研究中，我们表明，连续 5 天每天口服 10mg/kg 的 MeHg 会导致精子计数减少和精子运动能力受损。值得注意的是，MeHg 损害了大鼠的曲细精管，并增加了大鼠 GCs 的细胞凋亡指数。此外，MeHg 处理后自噬标志物微管相关蛋白轻链 3-II（LC3-II）和 beclin-1 的水平显著增加，可能通过抑制磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（Akt）/哺乳动物雷帕霉素靶蛋白（m-TOR）信号通路。此外，这些作用伴随着活性氧（ROS）的过度产生和抗氧化酶超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）和过氧化氢酶（CAT）的表达降低。有趣的是，MeHg 的补充会在大鼠睾丸中诱导氧化 DNA 损伤。总之，我们的数据表明，MeHg 通过氧化应激和自噬刺激 GC 凋亡，这可能是 MeHg 暴露后调节睾丸功能和分化的机制。
