脂肪酸代谢紊乱导致睾丸支持细胞（SC）功能受损和男性生育力下降。前期研究发现，与糖脂代谢功能相关的LncRNA TUG1（TUG1）在小鼠SC中有表达，提示TUG1可能影响SC功能，但具体的生物学功能和机制未明。本项目拟：①通过TUG1表达变化的观察、体外功能获得性和缺失性研究，明确TUG1在SC中的功能；②采用CRISRP/Cas9靶向基因编辑技术制备TUG1条件敲除小鼠，观察敲除鼠生殖功能变化（精子参数，影响SC功能的关键蛋白及基因）；③建立TUG1敲除SC细胞株，分析PPARγ的表达及定位，进而采用PPARγ激动剂或抑制剂，研究影响SC糖脂代谢及形成血睾屏障的关键蛋白变化；④利用miRNA芯片及Luciferace等技术，预测TUG1调节SC功能的相应靶分子并研究其潜在效应机制。本研究从LncRNA角度研究SC的功能及其内在调节机制，对男性不育的基础和临床研究具有深远的学术价值。

Disorders of fatty acid metabolism result in impaired function of testicular sertoli cell (SC) and decreased fertility in men. Previous studies have found the expression of LncRNA TUG1(TUG1) in mouse SC, which is involved in the function of glycolipid metabolism. This finding suggests that TUG1 may affect SC function, but its detailed biological functions and mechanisms are still unknown. This project is intended to: 1, Observe the changes of TUG1 expression and conduct functinal gaining or losing studies to demonstrate the roles of TUG1 in SC in vitro. 2, Establish TUG1 conditional knockout mice model by using CRISRP/Cas9 targeted gene editing technology and observe the changes of reproductive function in mouse (sperm parameters, expression of key proteins and genes affecting SC function). 3, Establish TUG1 knockout SC cell line, analyze the expression and localization of PPARγ, then study the changes of key protein affecting SC glycolipid metabolism and blood testis barrie with PPARγ agonist or inhibitor. 4, Explore potential molecular mechanisms underlying TUG1-mediated changes in SC with technologies of miRNA microarray, Luciferace and RNA-pull down et al. In our research, we aim to study the intrinsic regulation mechanism of LncRNA on SC function, which may have profound academic value for the basic and clinical research of male infertility.