全氟辛酸(PFOA)可导致男性生殖功能损伤，其具体机制尚不明确。Nrf2在调节应激反应中具有关键作用。我们前期实验发现PFOA抑制了Nrf2的表达，并导致睾丸组织氧化应激。据此，我们推测“以Nrf2为核心的抗氧化防御系统对PFOA的睾丸毒性具有调控作用”。本项目拟在器官、细胞及分子水平探讨PFOA对雄性小鼠生殖系统的毒性损伤作用机制，重点关注PFOA生殖毒性与生殖细胞凋亡和自噬的相关性，并通过Nrf2信号通路的激活和抑制观察Nrf2系统对PFOA诱导的睾丸生殖细胞损伤的保护作用。从基因转录、蛋白质表达和活性水平测定Nrf2及其下游抗氧化酶基因的表达，并通过检测凋亡和自噬相关基因的表达阐明Nrf2系统对生殖细胞氧化应激、凋亡和自噬的保护作用，从而揭示PFOA引起睾丸生殖细胞损伤的分子机制，以及Nrf2通路对PFOA生殖毒性的调控作用。为防治全氟化合物引起的精子发生异常和男性不育提供新的靶点。

Perfluorooctanoic acid (PFOA) exposure leads to male reproductive function damage. However, the specific mechanism of PFOA action is unclear. Nrf2 plays a key role in the regulation of stress response. Our previous study found that PFOA exposure inhibited Nrf2 expression and induced oxidative stress in the testicular tissue. Therefore, we speculate that Nrf2-dependent antioxidant defense system plays a role in regulating PFOA-induced testicular toxicity. In this study, the male reproductive toxicity of PFOA will be evaluated at organ, cell and molecular levels with emphasis on the relationships of PFOA-induced testicular toxicity to germ cell apoptosis and autophagy. Furthermore, the activation and inhibition of Nrf2 signaling pathway were induced to investigate the protective effect of Nrf2 on PFOA-caused testicular damage. Moreover, the expression and activity of Nrf2 and its targeted antioxidant enzyme genes were determined and the expression of apoptosis-related genes and autophagy-related genes was detected to analyze the effects of Nrf2 system on germ cell oxidative stress, apoptosis and autophagy. These studies will reveal the molecular mechanisms of PFOA action and regulatory effects of Nrf2 signaling pathway on PFOA-induced testicular toxicity, and provide a new target for the prevention and treatment of abnormal spermatogenesis and male infertility caused by perfluorinated compounds.