配子发生异常是导致不孕不育的主要原因之一。减数分裂是生殖细胞特有的分裂方式，它是单倍体配子形成的关键环节。生殖细胞有丝分裂向减数分裂的精准转变是启动减数分裂的首要条件，但是调控该过程的具体分子机制目前还不清楚。利用小鼠性腺体外培养系统，本项目初步发现H3K9me2在雌性生殖细胞有丝分裂向减数分裂转变过程中发挥重要作用。本项目将利用Stella-GFP转基因小鼠和G9a敲除小鼠模型，结合RNA-seq和ATAC-seq技术深入挖掘雌性生殖细胞有丝分裂向减数分裂转变过程中H3K9me2调控的关键因子。进一步通过ChIP-seq验证多能性相关基因的表达关闭是否直接依赖于基因调控区域的H3K9me2修饰，阐明H3K9me2调控雌性生殖细胞有丝分裂向减数分裂转变的确切功能和分子机制。本项目在理论上将为深入研究减数分裂启动的作用机制提出新的方向，在临床上将为治疗卵巢早衰、提升卵子质量等提供理论指导。

Abnormal gametogenesis is one of the main causes of infertility. Meiosis is a germ cell-specific division that is indispensable for generation of haploid gametes. The precise transition from mitosis to meiosis is the primary condition for meiotic initiation in germ cells. However, the underlying regulatory mechanisms still remain elusive. In this investigation, we preliminarily have found that H3K9me2 plays an important role in the transition from mitosis to meiosis of female germ cells by using an in vitro gonad culture system. To further explore the key factors regulated by H3K9me2 in the transition from mitosis to meiosis of female germ cells, Stella-GFP transgenic mouse model and G9a knock-out mouse model will be used, combined with RNA-seq and ATAC-seq technologies. Furthermore, ChIP-seq will be used to verify whether shutting down the expression of pluripotent genes is directly dependent on H3K9me2 modification in the gene regulatory region, and to clarify the exact function and molecular mechanism of H3K9me2 in regulating the transition from mitosis to meiosis of female germ cells. The findings of this proposed project will provide a new direction for the in-depth study of meiotic initiation theoretically, and a theoretical guidance for the treatment of premature ovarian failure and the improvement of oocyte quality clinically.