Methylmercury-induced testis damage is associated with activation of oxidative stress and germ cell autophagy.

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.