滋养细胞的上皮-间质转化（EMT）- - 上皮型细胞滋养细胞（CTB）转分化为间质型绒毛外滋养细胞（EVT）的过程，是胚胎成功植入子宫、建立母胎间联系的重要事件，其异常可引起EVT细胞侵袭能力降低，与子痫前期（PE）的发生关系密切。本研究提出"缺氧/复氧应激产生的ROS经DNA甲基化的协同调控作用诱导滋养细胞EMT异常"可能是PE发生的新机制。研究将探明生理性缺氧对CTB细胞EMT过程和细胞侵袭能力的促进，阐明病理性缺氧/复氧对EVT细胞MET过程的诱导以及对血管内皮的损伤，并深入探究HIF-1α、DNMT调控的基因启动子甲基化、PI3K/AKT和Wnt/β-catenin信号通路以及相关转录调控因子等在此过程中的介导作用，从而阐明缺氧诱导DNA甲基化调控的滋养细胞EMT过程在滋养细胞侵袭能力改变和PE发生中的意义，为PE发生的机制研究、可能的早期诊断指标或干预的新靶点提供思路。

In the course of placentation, cytotrophoblast (CTB) differentiating into extravillous trophoblast (EVT), undergoing an epithelial- mesenchymal transition (EMT), is vital for successful pregnancy. The failure of EMT in trophoblast leads to decrease in EVT invasion into uterus and might have close association with pathogenesis and progression of preeclampsia (PE). Based on previous researches by other scientists and our preliminary results, we postulate that ROS produced by hypoxia/reoxygenation stress leads to failure of EMT in trophoblast through co-regulation of DNA methylation. This might be one of potential mechanism of pathogenesis of PE. To establish this hypothesis, we will explore the effects of physilogical hypoxia, pathological hypoxia/reoxygenation on EMT or MET in trophoblasts. We will also study the roles of hypoxia induced factor 1α(HIF-1α), DNA methyltransferases (DNMTs) and their regulated genes through DNA methylation, signal pathways of PI3K/AKT and or Wnt/β-catenin in hypoxia induced EMT or MET in trophoblast. The association among hypoxia effects, DNA methylation regulated gene functions, abnormal transion of epithelial to mesenchymal in trophoblasts, shllow invasion of EVT and endovascular injury in PE will be evaluated in this research. We here provide new ideas in studying the mechanism of PE, potential eraly diagnostic markers or intervention targets on PE.