存在于母胎界面胚胎滋养细胞的HLA-G与母体蜕膜NK细胞之间的相互作用对于维持早期妊娠具有重要作用，二者功能失调会导致复发性流产（RSA）。本课题组前期研究发现，miR-133a可负调控HLA-G的表达，HLA-G下调使蜕膜NK细胞促侵袭和促血管生成功能受损，这可能是RSA发生的重要原因。但下调的HLA-G引起蜕膜NK细胞功能失调的具体机制尚未阐明。含HLA-G外泌体可存在于胎盘和孕妇外周血中，对维持正常妊娠具有重要作用；因此，我们提出假说：RSA孕妇母胎界面和外周血含HLA-G的外泌体分泌异常，影响了蜕膜NK细胞功能，导致RSA发生。拟在前期研究基础上，选用孕早期流产绒毛组织、母体蜕膜组织及外周血样本、RSA小鼠模型等为材料，通过细胞学、免疫学等方法探索含HLA-G外泌体参与早期RSA的机制。本研究以期在分子与细胞层面揭示RSA发生的新机制，可望为临床精准预防和治疗RSA提供靶点及策略。

The interaction between trophoblast HLA-G and decidual NK (dNK) cells on maternal-fetal interface plays a vital role in the maintance of early-term gestation, and the dysregulation of both can cause recurrent spontaneous abortion (RSA). Our previous study showed that decrease of HLA-G induced by miR-133a in trophoblast cells can disturb the proinvasion and proangiogenesis potential of dNK cells, which may be an important cause of RSA. However, the specific mechanism of down-regulation of HLA-G-induced dysfunction of dNK cells remains unclear. HLA-G-expressing exosomes which can exist in maternal blood and maternal-fetal interface are important to the normal pregnancy. Therefore, we hypothesize that abnormal secretion of HLA-G-expressing exosomes derived from maternal-fetal interface and peripheral blood of RSA patients interferes with the function of dNK cells and disturbs trophoblast invasion and uterine spiral arteries remodeling, then finally leads to RSA. On the basis of previous study, we will use early abortion chorionic villi; maternal decidua and peripheral blood samples; RSA mouse models as materials, by adopting cytology and immunology techniques to explore the mechanism that HLA-G-expressing exosomes are involved in early-term RSA. This study aims to reveal the new mechanism of RSA occurrence at the molecular and cellular levels, which is expected to provide targets and strategies for the clinical precise prevention and treatment of RSA.