复发流产（RSA）与母胎免疫调节紊乱相关，常表现为蜕膜免疫细胞（DIC）表型与功能异常。早孕期蜕膜NK细胞（dNK）作为占比最高的DIC，参与调节子宫内膜蜕膜化、滋养细胞侵袭、胎盘血管重铸和母-胎免疫耐受等过程，但其在蜕膜局部分化发育的分子机制至今未明。我们前期研究发现人正常早孕母-胎界面高表达RANKL，可诱导COX-2+dNK分化，进而促进滋养细胞侵袭，而RSA患者蜕膜RANKL低表达，COX-2+dNK比例下降；RANKL基因敲除孕鼠子宫COX-2+NK杀伤活性增强，胚胎吸收率升高，据此我们提出科学假说“母-胎界面RANKL低表达诱导COX-2+dNK分化异常致RSA”。本研究以体外模拟母-胎界面微环境和体内动物实验为研究手段，拟阐明RANKL调节COX-2+dNK分化的分子机制及其异常致RSA的病理机制，为母-胎免疫耐受机制研究提供新方向，为探索诊治RSA的新策略提供科学依据。

Recurrent spontaneous abortion (RSA) is associated with maternal-fetal immunomodulatory disorders, often manifested as abnormal function and phenotype of decidua immune cells (DIC). Decidua NK cells (dNK), as the highest proportion of decidua immune cells, are involved in promoting endometrial decidualization, regulating trophoblast invasion, placental vascular remodeling and maternal-fetal immune tolerance, but the specific mechanism of the differentiation and development of dNK cells has not been elucidated yet. Our previous study found that high expression of RANKL in maternal-fetal interface of normal early pregnancy could promote the differentiation of COX-2+dNK and further facilitate the invasion of trophoblast cells, while the expression of RANKL in decidua of RSA patients decreased with lower proportion of COX-2+dNK cells. The cytotoxity of uterine COX-2+NK cells of RANKL knockout mice enhanced with embryo absorption rate increased. Based on these results, we proposed a scientific hypothesis that low expression of RANKL at maternal-fetal interface induces abnormal differentiation of COX-2+dNK, leading to recurrent abortion. Therefore, taking advantage of in vitro trials for imitating the maternal-fetal microenvironment and in vivo animal experiments, our study tends to investigate the molecular mechanism of the differentiation of COX-2+dNK induced by RANKL and the pathogenesis of abnormal RSA, so as to provide a new direction for researching the mechanism of maternal-fetal immune tolerance and to explore a scientific basis for the new strategy for the diagnosis and treatment of recurrent miscarriage.