睾丸细胞外泌体miRNAs调控精原干细胞分化的作用及机制研究

精原干细胞（SSC）分化是决定雄性生殖的关键，其分化过程受睾丸微环境的精细调控。但微环境中调节因子的组成及其对SSC分化的作用及机制远未彻底阐明。外泌体携带的miRNAs广泛参与细胞增殖、凋亡、分化等生物学过程，是细胞微环境的重要组成。前期研究表明，睾丸体细胞来源外泌体对SSC的分化具有促进作用，同时miRNA芯片结果提示miRNA可能是外泌体参与调控SSC分化的关键因素。基于上述科学问题，项目拟运用高通量测序、细胞生物学和分子生物学等方法系统地研究睾丸微环境中的外泌体对SSC的分化调控作用，明确其中起作用的关键miRNAs及其作用靶点，阐明外泌体miRNAs调控SSC分化的分子机制。为SSC发育和分化提供新的调控理论基础，为男性不育症的诊治提供新靶点，对揭示精子发生的分子机理、降低不孕不育率、预防子代遗传缺陷等都有重大意义。

The differentiation of the spermatogonial stem cell (SSC) is the critical step for male reproduction. The process of differentiation is regulated by the microenvironment of the testis. However, the mechanisms by which microenvironment factors commit to SSC differentiation are still unclear. Exosome-miRNAs take part in the regulation of various biological processes such as cell differentiation, proliferation, and apoptosis. It is an important component of microenvironment. The project preliminary studies shows that exosome derived testicle cells promoting the differentiation of SSC. And miRNA microarray data suggested that exosome miRNA may played an important role in the differentiation of SSC. In this study, we will systematically study role of the exosomes miRNA in the differentiation of SSC by using the approaches for molecular biology and cell biology and high-throughput sequencing. Thourgh our study, we are expecting to disclose the mechanism of exosome miRNAs in SSC differentiation, which would provide novel mechanisms underlying spermatogenesis and are of great significance in treating male infertility and preventing defect of offspring.