研究显示绒毛外滋养层细胞（EVT）适度侵袭蜕膜、参与着床和子宫螺旋动脉血管重塑。发生功能异常时可导致流产或妊娠高血压综合征等疾病，甚至危及母、儿生命。本课题组在国家杰出青年基金等资助下研究发现，转录因子YY1与HOTAIR相互作用构成信息转导轴，通过精细机制调控基质金属蛋白酶（MMPs）等分子的功能，进而调控EVT侵袭力。其中涉及RNA结合蛋白PUM1功能以及MMP2启动子区结合特性改变等机制。具体机制尚不清楚。本项目拟在此基础上深入研究转录前调控和RNA结合蛋白等调节EVT功能的机制。科学假说：YY1针对关键分子启动子区的转录调控、通过RNA结合蛋白参与的机制，调节MMP及其内源性拮抗物TIMP平衡，维持EVT正常迁移和侵袭功能，确保妊娠成功。预期研究结果将为解析妊娠相关疾病机制、实现精准防治提供科学依据。

Extravillous trophoblast (EVT) is critical for blood vessel remodeling during implantation and placenta development. Impaired function of EVT may result in miscarriage and preeclampsia and even be vital to mother and fetus. Our group recently found that YY1 controls EVT invasion via modulating MMPs function. MMP2 promotor binding function of YY1 is important, and RNA binding proteins are involved. Detailed mechanism remains unclear. In the present study, we will focus on the mechanism by which EVT functions are modulated. Our hypothesis: YY1 specifically binds to promotor binding sites, works together with RNA-binding protein, keeps MMP and tissue inhibitor of MMP (TIMP) balance and permits adequate EVT migration and invasion into decidua, thus leads to pregnancy success. Pre-transcriptional factors and RNA-binding proteins may be involved and play key roles. This study will provide clues for further understanding of the mechanism of pregnancy-related diseases and beneficial for establishing precise prevention and therapy.