锰属于环境内分泌干扰物（EEDs），是常见的职业毒物。据报道，锰对生殖毒性具有氧化损伤作用，但机制尚不清楚。流行病学调查显示，锰作业的工人，可发生严重的、不可逆的生殖损伤。在镉等的生殖研究，自噬是氧化损伤机制之一，而Nrf2/ARE是体内最重要的抗氧化信号通路，且两者具有共同激活途径。基于锰可致睾丸细胞损伤，与镉同属二价离子和EEDs，提出自噬和Nrf2/ARE信号通路可能是锰致睾丸细胞氧化损伤机制的假设。拟选择自噬频率最高的Leydig 细胞作为研究对象，探索自噬与Nrf2/ARE信号通路在锰致Leydig细胞氧化损伤中表达的特点，利用抑制剂与激动剂研讨其参与调控的机制及相互作用的关系；筛选出一些关键蛋白，用动物实验佐证其在锰致Leydig细胞氧化损伤中的作用。通过研究将为进一步揭示锰致雄性生殖毒性机制提供科学依据，并为寻找生殖毒性新的生物标志、抑制剂和激活剂等相关防治措施提供研究基础。

Manganese (Mn), belonging to the environmental endocrine disruptors（EEDs）, is a common occupation poison. Data showed that Mn induces oxidative damage in the reproductive system, but the underlying mechanisms are poorly understood. Occupational epidemiologic studies indicated serious and irreversible reproductive injury after Mn exposures. Evaluation of reproductive oxidation for some EEDs such as cadmium suggests mechanism of autophagy and Nrf2/ARE signaling pathway, and they have shared activation pathway. Mn as another divalent ions in EEDs which causes toxicity in esticular cells, it is likely that autophagy and Nrf2/ARE signaling pathway can also work. This study aimed to investigate the characteristics of autophagy and Nrf2/ARE signaling pathway activation in the process of Mn induced Leydig cell(chosen for high autophagy rate) injury by cell experiment, and its regulation mechanism would be explored with autophagy inhibitors, and Nrf2 agonists and inhibitors. Some key protein in autophagy and Nrf2/ARE signaling pathways would be filtered, and their effects in the oxidative damage of Leydig cells induced by Mn would be further confirmed with animal experiment. Such findings will provide a scientific basis for further revealing the mechanism of male reproductive toxicity induced by Mn. It would also be meaningful to the research of new biomarkers, autophagy inhibitors and Nrf2 activators in reproductive toxicity.