不明原因复发性流产（URSA）是人类妊娠常见合并症。母胎界面滋养细胞侵袭不足是流产发生的关键。我们前期研究发现PVT1通过调控Wnt2信号影响滋养细胞侵袭力参与URSA的发生，但具体机制不明。文献报道，PVT1可作为ceRNA竞争性结合miR-199a-5p调控肿瘤细胞的侵袭力；而miRNA-199a-5p可通过调控Wnt2信号影响肿瘤细胞迁移。因此，我们推测在妊娠过程中，PVT1以ceRNA方式竞争性结合miR-199a-5p来调控Wnt2信号，影响滋养细胞侵袭力，导致流产的发生。本项目拟在细胞水平通过基因转染、RIP等实验深入阐明PVT1-miR-199a-5p-Wnt2环路对滋养细胞侵袭力的调控作用及分子机制；构建复发性流产小鼠模型，验证环路相关分子对妊娠过程的影响；在组织水平进一步证明环路对妊娠结局的影响。本研究深入探索URSA发生的分子事件，为URSA的防治提供新的干预靶点。

Unexplained recurrent spontaneous abortion is a common complication of human pregnancy. The inadequate invasion of trophoblast cells in maternal-fetal interface is the key to the occurrence of abortion. Our previous study found that PVT1 was involved in the occurrence of URSA by regulating the invasiveness of trophoblastic cells by regulating Wnt2 signals, but the specific mechanism was unknown. It is reported that PVT1 can act as ceRNA binding miR-199a-5p to regulate the invasiveness of tumor cells, while miRNA-199a-5p can affect the migration of tumor cells by regulating Wnt2 signals. Therefore, we speculate that in the course of pregnancy, PVT1 can regulate Wnt2 signaling act as ceRNA competitively binding miR-199a-5p and affect the invasiveness of trophoblastic cells, leading to the occurrence of miscarriage. The aim of this project is to elucidate the regulatory role and molecular mechanism of PVT1-miR-199a-5p-Wnt2 loop in trophoblastic cell invasiveness at cellular level through gene transfection and RIP experiments. Constructing mouse models of recurrent abortion to verify the effect of loop related molecules on the pregnancy process, and further proving the effect of the loop on the pregnancy outcome at the tissue level. This research is to explore the molecular events of URSA and to provide new targets for the prevention and treatment of URSA.