小鼠支持细胞Rac1基因缺失导致减数分裂异常的分子基础及机制

精子发生过程中，减数分裂期精母细胞需与支持细胞保持密切联系，以依赖于支持细胞提供的支持、营养和信号作用。我们前期研究发现，支持细胞Rac1基因敲除后，青春期小鼠精母细胞减数分裂异常，睾丸变小且成年小鼠不育。但是支持细胞提供何种信号，如何调节精母细胞的减数分裂，目前尚不清楚。本项目以支持细胞Rac1特异敲除小鼠为模型，利用分子细胞遗传学方法进一步研究Rac1在精子发生中的作用；并在此基础上结合赖氨酸异构酶转基因小鼠模型，利用蛋白质组学和生物信息学等技术，发现支持细胞来源的分子，通过功能鉴定，筛选其中影响减数分裂的分子，以期阐明支持细胞调节减数分裂的分子机理，揭示精子发生异常的新机制；最终为支持细胞异常引起的少精子症、无精子症的预防、诊断和治疗提供科学依据。

In spermatogenesis, Sertoli cells provide support, nutrition and signals for spermatocytes, suggesting the critical function of Sertoli cells in meiosis. Previously, we found that Rac1 deletion in Sertoli cells leads to abnormal meiosis, smaller testis in prepubtal mice and infertility in adult males. However, the molecular regulation mechanisms of Sertoli in meiosis are unclear. In this project, we will contine to employ Rac1 conditional knockout mouse model to study the Rac1 function in spermatogenesis. Combining with the Lysine recemase transgenic mice, we will uncover the molecules secreted from Sertoli cells through proteomic and bioinformatic methods. Furthermore, we will sort out the proteins associated with meiosis by functional screening experiments. Our work will reveal the regulation mechanism of Sertoli cells in spermatocytes’ meiosis, and provide new scientific evidence for the precaution, diagnosis and cure of Sertoli cell abnormality-induced oligozoospermia or azoospermia.