基于BMP信号通路的早期性腺体细胞调控生殖细胞减数分裂启动的机制研究

减数分裂是生殖细胞特有的一种细胞分裂方式，是配子发生过程中的一个关键环节。减数分裂启动的调控机制是目前生殖生物学和发育生物学领域的研究热点。生殖细胞异常减数分裂是诱发不孕不育的重要因素，但是具体的调控机制尚不清楚。我们前期研究发现，在小鼠早期睾丸支持细胞中激活β-catenin信号通路导致雄性生殖细胞在胚胎期异常启动减数分裂；体外细胞重聚实验证明早期雌性性腺体细胞能够诱导雄性生殖细胞启动减数分裂；进一步的转录组分析显示BMP信号通路可能在生殖细胞减数分裂启动过程中发挥重要作用。本研究拟在前期工作的基础上，利用基因敲除小鼠模型，结合细胞生物学、分子生物学，以及组学等研究方法，明确BMP信号通路在减数分裂过程中的生理功能，挖掘BMPs在减数分裂启动过程中调控及协同作用因子，探明性腺体细胞调控生殖细减数分裂的分子机制，为阐明减数分裂启动的调控机制和临床治疗相关生殖疾病提供理论支持。

Meiosis is a type of cell division unique to germ cells, and is a key process of gamete development. The regulation of meiosis initiation is a hot topic in the field of reproductive and developmental biology. Germ cell abnormal meiosis is an important factor inducing infertility, but the specific regulatory mechanism is still unclear. Our previous study find that over-activation of the β-catenin signaling pathway in Sertoli cell leads to the ectopic initiation of meiosis in male germ cells during embryonic stage; In vitro cell re-aggregation experiments show that early female gonadal somatic cells can induce male germ cells to initiate meiosis; further transcriptome analysis shows that BMP signaling pathway may play an important role in the process of germ cell meiosis initiation. Based on the previous work, this study intends to use the knockout mouse model, combined with cell biology, molecular biology, and omics, to determine the physiological function of BMPs during meiosis. This research is for mining the regulatory and synergistic factors of BMPs in the process of meiotic initiation, exploring the molecular mechanism of gonadal cells regulating reproductive meiosis, and providing theoretical support for clarifying the regulatory mechanism of meiotic initiation and clinical treatment of reproductive diseases.