精原干细胞（SSC）的增殖和自我更新，高度依赖Sertoli细胞分泌因子等微环境的严密调控。然而应用已知细胞因子，无法实现人SSC长期培养扩增，更无法获得SSC来源的成熟精子。课题组前期研究发现FGF5在唯支持细胞综合征患者Sertoli细胞表达异常降低，并证实FGF5能激活ERK1/2和PI3K/AKT通路，促进SSC体外增殖，这提示FGF5在SSC命运调控中发挥关键作用。然而其分子机制尚未阐明。本课题拟：1）明确FGF5及其受体在人睾丸组织的定位与表达特征；2）在Sertoli细胞与SSC共培养体系中，采用基因过表达或沉默技术，探讨FGF5如何调控SSC增殖和自我更新；3）应用生精小管注射和生精小管异位重建技术，揭示FGF5在体内对SSC的影响。本课题将揭示FGF5调控SSC命运的分子机制，有助于优化SSC的培养体系，阐释精子发生障碍的机理，提供生精功能损伤修复及无精子症诊治的新靶点。

The proliferation and self-renewal of spermatogonial stem cell (SSC) highly depend on the strict regulation provided by the Niche, which is mainly composed of growth factors secreted by Sertoli cells. However, human SSC cannot be cultured and differentiated to mature sperm in vitro using growth factors known. Our previous studies have revealed that the expression of FGF5 in Sertoli cells from Sertoli cell-only syndrome patients is significantly lower than that from men with normal spermatogenesis. Further studies demonstrate that FGF5 promotes the proliferation of SSC in vitro via activating ERK1/2 and PI3K/AKT pathway, indicating that FGF5 plays crucial roles in the fate determination of SSC. However, the underlying molecular mechanisms remain unknown. Therefore, we will conduct this important project with the following aims: i) to validate the expressions characteristics of FGF5 and its receptors in human testes; ii) to explore the effects of FGF5 exerted on the proliferation and self-renewal of SSC using gene overexpression and silencing techniques via in vitro Sertoli cell and SSC co-culture system; iii) to reveal the biological effects of FGF5 in vivo using seminiferous tubule transplantation and ectopic seminiferous tubule regeneration models. Eventually, the molecular mechanisms involved in SSC proliferation and self-renewal could be elucidated. The present study is of particular significance, because it could optimize the human SSC culture system, underlie a novel pathological mechanism of spermatogenic dysfunction and, further offer new targets for the repair of spermatogenic damage and the management of azoospermia.