胎盘发育不良与蜕膜化障碍致早期妊娠失败的分子机制及其干预研究

正常妊娠的建立和维持依赖母-胎之间的互作与适应，其中子宫内膜蜕膜化与胎盘的正常发育是其关键。一旦蜕膜化进展障碍、胎盘形成不良将导致妊娠失败如自然流产。自然流产发病率高，缺乏有效防治策略。我们前期研究发现：母-胎界面滋养细胞与蜕膜免疫细胞和蜕膜基质细胞协调对话调控子宫蜕膜化进程与胎盘正常发育，母-胎对话失调将导致妊娠失败，本项目围绕妊娠过程的关键生物学事件（子宫内膜蜕膜化与胎盘发育），利用人体标本与小鼠模型，通过组学筛选与信息学分析、一系列细胞与分子生物学、免疫学技术，从体内、体外、ex vivo系统研究母-胎界面功能细胞协作调控子宫内膜蜕膜化进程与胎盘发育过程，并解析异常调控引发胎盘发育不良与蜕膜化障碍的分子机制，进一步探讨母-胎异常对话致妊娠失败的分子机制，从生理与病理方面阐述母-胎对话在妊娠中的关键作用，并探索妊娠失败与妊娠并发症的早期预警与干预策略，以期改善母婴健康。

The maternal-fetal cross-talk and mutual adaptation are essential for the establishing and sustaining of a successful pregnancy, during which the decidualization of endometrium and the normal development of placenta are two keyfactors. Failure in decidualization or malformation of placenta would lead to pregnancy failure including miscarriage. Miscarriage is a common disease but lacks effective strategies for prevention and treatment. Our previous study reveals that the cross-talk between the embryonic trophoblasts and maternal decidual immune cells and stromal cells helps to modulate the progression of decidualization and placenta development, while the dysregulation of the cross-talk would cause pregnancy failure. In this project we focus on the key events during the course of pregnancy (endometrium decidualization and placenta development), and utilize human clinical samples, mouse models and techniques of omics, bioinformatics, cellular and molecular biology and immunology, to systematically study in vivo, in vitro and ex vivo how the cells at the maternal-fetal interface regulate the progression of decidualization and placenta development, and to elucidate how the dysregulation causes failure in decidualization and placenta development and further leads to pregnancy failure. We hope to demonstrate the importance of maternal-fetal cross-talk from physiological, pathological and molecular perspectives, and hope to see it transferred to clinical strategies for the diagnosis and treatment of pregnancy failure and complications, in order to improve health for both mother and fetus.