Leydig细胞功能受损是肥胖导致生精障碍的重要原因。cAMP-蛋白激酶A（PKA）信号轴紊乱是肥胖诱发Leydig细胞功能受损的关键机制之一。申请人新近发现，新型脂肪因子C1q/肿瘤坏死因子相关蛋白6（CTRP6）高表达于睾丸Leydig细胞中，肥胖小鼠睾丸组织和Leydig细胞中CTRP6表达显著下调；进一步沉默CTRP6后，Leydig细胞内cAMP含量、PKA活性和睾酮分泌均下降。结合文献报道，我们提出科学假说：肥胖下调Leydig细胞中的CTRP6，导致Leydig细胞内cAMP-PKA信号轴活化受阻，睾酮分泌水平降低，进而影响男性生育能力。本项目结合前期工作，利用Leydig细胞CTRP6条件性敲除小鼠，探讨CTRP6对肥胖小鼠Leydig细胞及生精功能的影响及机制。本研究旨在寻找男性不育症临床治疗的新靶点和新策略。

Dysfunction of Leydig cells is one of the important reasons of obesity-induced spermatogenesis deficiency. Disturbance of cAMP-protein kinase A (PKA) signal axis is a critical mechanism for obesity-induced dysfunction of Leydig cells. We recently found that C1q / tumor necrosis factor-related protein 6 (CTRP6) was highly expressed in Leydig cells of the testis. CTRP6 expression in testicular tissue and Leydig cells of obese mice were down-regulated. We also found that the cAMP content, PKA activity, and testosterone secretion of Leydig cells were decreased after CTRP6 silencing. Based on previous reports and our findings, we proposed our hypothesis: decreased CTRP6 expression in Leydig cells caused by obesity resulted in impairment of cAMP-PKA signaling pathway and reduction of testosterone secretion, which affected male fertility. In this project, Leydig cell-specific CTRP6 knockout mice were used to explore the role and mechanism of CTRP6 on Leydig cells and spermatogenic function in obese mice. This research aims to find new targets and provide new ideas for the clinical treatment of male infertility.