Activin A和miR503协同调控卵原细胞减数分裂起始的分子机制

哺乳动物雌性生殖细胞减数分裂启动的机理研究鲜有报道，本项目组借助小鼠卵母细胞体外发育模型已初步发现Activin A（ActA）可以促进卵原细胞启动减数分裂并发育成熟。本项目将利用Stra8-mCherry和Oct4-Δ-GFP双转基因小鼠模型，通过RNA-seq技术挖掘卵原细胞减数分裂启动的关键基因和miRNAs。深入研究miR503协同ActA调节Cyp26b1表达，共同影响减数分裂启动关键基因Stra8的表达，调控卵原细胞启动减数分裂的分子机制。探讨孕体ActA和雌激素水平、胎儿卵巢视黄酸（RA）水平等内分泌变化与miR503表达变化的关系，描绘miR503通过调节ActA受体表达而实现负反馈调节ActA功能的作用途径。本研究将丰富ActA和RA等内分泌变化调节生殖细胞减数分裂启动的理论，加强人们对卵母细胞发生相关分子事件的认识，为早期生殖细胞向卵母细胞有效转变提供理论和技术支持。

The regulatory mechanism of germ cell meiotic initiation has rarely been reported. Our preliminary research has found that ActA can promote the meiotic entry and further oocyte maturation using an in vitro mouse oogenesis model. The present study aims to uncover the meiotic initiation-specific miRNAs and microRNAs with RNA-seq technology, using Stra8-mCherry and Oct4-Δ-GFP double transgenic mouse model. We will investigate the mechanism of Cyp26b1 expression regulated by ActA and miR503, which have a combined impact on the expression of meiosis initiation-specific gene Stra8 and the regulation of meiosis initiation duing oogenesis. Futhermore, we will study the relationship between the level of ActA and estrogen in pregnant mice, as well as the level of retinoic acid (RA) in fetal mouse ovary, and the expression of miR503, depicting the pathway of how miR503 exerts its negative feedback function to ActA by adjusting the ActA receptor expression. This research will enrich the theory about the meiosis initiation of female germ cells regulated by expression of ActA and RA, and strengthen our understanding on the molecular events of oogenesis. In practice, this study will also provide theoretical and technical support for the differentiation from early germ cells into oocytes in vitro.