妊娠的建立和维持是在生殖内分泌-免疫微环境调控下，由多种细胞和众多生物活性分子相互作用介导的极其错综复杂的交互对话与协同作用。我们前期研究发现滋养细胞通过表达CXCL12,TSLP等诱导母-胎免疫耐受，提示滋养细胞在母-胎间交互对话及母-胎免疫耐受形成中起核心作用。一旦母-胎界面内分泌-免疫调节功能异常，将导致妊娠失败，子痫前期等妊娠相关疾病。但人们对于母-胎界面免疫耐受状态建立和维持的确切分子机制以及母体生殖内分泌微环境如何调节母体免疫细胞分化与耐受胚胎抗原？仍知之甚少。因此本项目将以早期妊娠失败和子痫前期作为主要研究对象，解析母-胎界面微环境通过加强母-胎交互对话训导母-胎免疫耐受的分子机制，进而揭示母-胎免疫耐受紊乱致早期妊娠失败和子痫前期的病理机制。解答这些科学问题，不仅对于阐明母-胎免疫耐受机制具有重要意义，而且对于揭示妊娠相关疾病的发病机制及探索防治新策略亦具有重大指导意义。

Under the control of in reproductive endocrine-immune microenvironment, the establishment and maintenance of pregnancy are archived by the complicated dialogue and synergistic effects, which are mediated by a variety of cells and many bioactive molecular interactions. Our previous study found that trophoblast cells induce maternal-fetal immune tolerance through expression of CXCL12 and TSLP, suggesting that trophoblast cells play a central role in the cross-talk between fetus and mother and the information of maternal-fetal immune tolerance. Once the disorder of endocrine-immune regulation at the maternal-fetal interface will lead to pregnancy associated diseases, such as pregnant failure, preeclampsia. But little is known about the exact molecular mechanism for the establishment and maintenance of maternal-fetal immune tolerance, and how reproductive endocrine microenvironment regulates maternal immune cell differentiation and tolerance to embryo antigen. Therefore, in this project, we will use early pregnant failure and preeclampsia as the main object, and explore the molecular mechanisms of microenvironment at maternal fetal interface on maternal-fetal immune tolerance by strengthening maternal-fetal interaction dialogue, and further reveal the pathological mechanism of early pregnant failure and preeclampsia induced by the disorder of maternal-fetal immune tolerance. Answers to these problems, not only has an important significance for clarifying the mechanism of the maternal-fetal immune tolerance, but also has a great guiding significance for revealing the pathogenesis pregnancy associated diseases and exploring new strategies for prevention of pregnancy associated diseases.