复发性流产（RM）是临床难治性不育症，其发病与绒毛外滋养细胞（EVT）生理活性的异常密切相关。我们发现miR-3074-5p在正常妊娠小鼠母胎界面呈低表达，在RM患者绒毛中高表达；并证实它能诱导人EVT来源的HTR8/SVneo细胞凋亡并抑制其侵袭，且伴随p27蛋白表达上调。由此推测miR-3074-5p很可能通过干扰EVT的生理活性而导致妊娠失败。为验证此推测，本项目将检测miR-3074-5p对HTR8/SVneo细胞中p27信号通路相关蛋白表达水平的影响；观察miR-3074-5p的细胞生理学效应是否受p27信号通路抑制剂的影响；验证miR-3074-5p对小鼠早期妊娠的影响，及雌孕激素与miR-3074-5p表达的关系；通过筛查早孕妇女外周血中miR-3074-5p等的含量，分析其与RM的相关性，以期能阐明miR-3074-5p对EVT的调控作用机制，并发现新的RM生物标志分子。

Recurrent miscarriage (RM) is an adverse pregnancy outcome characterized by the dysfunction of extravillous trophoblast cells (EVT). Our previous research found that, the expression of miR-3074-5p was remarkably decreased at the maternal-fetal interface in mice, but significantly increased in the placental villus of RM, and the over-expression of miR-3074-5p in HTR8/SVneo cells promoted cell apoptosis but inhibited cell invasion, being accompanied by the significantly elevated expressions of p27. Thus, we hypothesized that, the up-regulated expression of miR-3074-5p might lead to the early pregnancy loss by disturbing the appropriate cellular activities of EVT.. To authenticate this hypothesis, in this study we plan to investigate the in vitro effects of miR-3074-5p on the expression levels of molecules involved in p27-pathway in HTR8/SVneo cells, as well as the effects of inhibitors of p27-pathway on the cellular physiological effects of miR-3074-5p; meanwhile, the in vivo effects of miR-3074-5p on the embryo implantation, and the effects of steroid hormone on the expression of miR-3074-5p at the maternal-fetal interface in mice will be also observed；Furthermore, the venous blood samples will be collected from RM patients and normal early pregnant women to evaluate the potential role of circulating miR-3074-5p and other miRNAs as novel biomarkers for RM.