男性因素引起的不孕不育症是临床常见疾病，主要表现为少、弱或无精子症。卵泡刺激素（FSH）治疗，部分患者症状改善，恢复生精功能。但是FSH调控雄性生殖细胞靶点不明，调控路径未知。我们前期的研究结果表明，在精原干细胞-支持细胞共培养体系中添加FSH，可以促进精原干细胞增殖；FSH的效应基因SF-1直接与精原干细胞增殖的关键细胞因子GDNF的启动子结合，促进GDNF转录。因此，我们认为：FSH是调控体内精原干细胞增殖的主要激素，其作用方式是通过支持细胞内SF-1调控GDNF表达，以旁分泌的方式影响雄性精原干细胞的增殖。本研究中，我们将通过凝胶迁移实验、基因定点突变、基因敲除动物模型等技术，分析SF-1调控体内精原干细胞增殖的机制、支持细胞与精原干细胞之间的相互作用，阐明精原干细胞体内发育的分子机制，为临床药物干预无精子症提供方案与依据。

Male factor infertility is a common disease mainly with spermatogenesis abnormalities including oligozoospermia, asthenospermia and azoospermia. Follicle stimulating hormone (FSH) treatment improved the recovery of spermatogenic function among some patients. The targets as well as regulatory pathways in male germ cells regulated by FSH are still unknown. Our previously reported results indicated that FSH promoted the proliferation of spermatogonial stem cells (SSCs) co-clutured with Sertoli cells and that FSH responsive genes,SF-1 directly binded to the promoter of GDNF which is a key gowth factor for SSCs self-renewal. Therefore, we suppose that FSH is the main hormone in regulation of the proliferation of SSCs in vivo and affects the GDNF expression by SF-1 within the Sertoli cells to improve the proliferation of male spermatogonial stem cell in paracrine manner. In the present study, many methods including co-immunoprecipitation, electrophoresis mobility shift assays, site-directed mutagenesis and gene knockout animal models will be used to analyze the regulation mechanisms of SF-1 on the proliferation of SSCs in vivo and the interactions between SSCs and Sertoli cells. It will clarify the molecular mechanisms of SSCs development in vivo to find out the pathological causes and provide new therapeutic targets for male infertility.