近年来，睾丸发育不全综合征(TDS)的发病率不断上升。研究表明TDS与邻苯二甲酸二丁酯（DBP）等环境内分泌干扰物引起的氧化应激相关，睾丸Sertoli细胞是重要靶细胞之一。我们前期发现Keap1-Nrf2通路参与调控Sertoli细胞的氧化应激损伤，但通路激活的机制尚不明确。同时DBP染毒后大鼠睾丸生精细胞和Sertoli细胞中泛素C端水解酶L1（UCH-L1）及Keap1表达水平降低，因此我们推测UCH-L1可能通过调控Keap1-Nrf2通路参与Sertoli细胞的氧化应激损伤。本课题拟从细胞水平研究UCH-L1对keap1和Nrf2表达的调控作用及具体机制，分析UCH-L1过表达、干扰表达和应用UCH-L1抑制剂后Keap1、Nrf2及下游分子表达变化，并在动物模型中验证上述改变，探讨UCH-L1在Sertoli细胞氧化应激损伤中的作用及机制，为TDS的分子机制研究提供新的方向。

Recently, the incidence of Testicular Dysgenesis syndrome (TDS) rises every year in our country. TDS has been proven to be associated with oxidative stress caused by endocrine-disrupting chemicals (EDCs), of which DBP is the most important one. Sertoli cells are one of the main target cells of oxidative stress. In our previous study, we found that Keap1-Nrf2 pathway is involved in the regulation of oxidative stress in Sertoli cells, but the mechanism is not clear. Further studies showed that DBP treatment caused the decrease of Ubiquitin C-terminal hydrolase L1（UCH-L1）and Keap1, which mainly located in spermatogenic cells and Sertoli cells. Thus, we propose a hypothesis the decrease of UCH-L1 led to the degradation of Keap1 and activated the expression of Nrf2, alleviating the oxidative stress caused by DBP in Sertoli cells. The purpose of our research was to investigate whether UCH-L1 can regulate the expression of Keap1 and Nrf2 in Sertoli cells and the molecular mechanism at cellular level, and analyzed adenovirus transfection and small RNA interference of UCH-L1 and expression changes of Keap1, Nrf2 and downstream molecules after application of UCH-L1 inhibitors. Meanwhile, the above changes were to be verified in animal model. Our research aims to investigate the role and mechanism of UCH-L1 in oxidative stress injury of Sertoli cells, and provide new therapeutic evidence for the study of the molecular mechanism of TDS.