Abstract
Recent researches have demonstrated that many nanoparticles are harmful to spermatogenesis. However, the reported nanoparticles -elicited testicular pathologies have been mostly confined to hormone levels and sperm quality and quantity, the detail mechanism is still largely unknown and the strategies to reduce the toxicity of nanoparticles on testis are lacking. Here, we found that CdSe/ZnS quantum dots (QDs) exposure impair double-strand break (DSB) repair in spermatocyte, leading to the disruption of meiotic progression and thus cell apoptosis and decreased sperm production. Furthermore, we found that QDs exposure elevates the autophagy. Crucially, both in vitro and in vivo studies indicated that elevated autophagy could down-regulate the expression of the genes responsible for homologous recombination, which is the main pathway for DSB repair during meiosis, indicating that spermatogenesis impairment by CdSe/ZnS QDs is mediated by autophagy. Consequently, injection of autophagy inhibitor (3-MA) restore DSB repair in spermatocytes, resulting in prevention of spermatocyte apoptosis and recovery of spermatogenesis. Our studies strongly indicate that autophagy is key for eliciting the spermatogenesis dysfunction after nanoparticle exposure, and autophagy inhibition can be used as a potential clinical remedy for alleviating the male reproductive toxicity of nanoparticles.