双酚A（BPA）是影响人类生殖健康的环境内分泌干扰物之一，环境水平BPA长期暴露可影响胚胎滋养细胞侵袭而降低着床率，但具体机制不清。滋养细胞上皮-间充质转化（EMT）是成功着床的关键，始于胚胎稳定粘附于子宫内膜时。推测母胎界面细胞间的接触可能是EMT的重要条件，而表达于细胞界面的Eph/ephrin家族很可能对胚胎EMT具有重要的调控作用。前期研究发现，BPA高暴露者子宫内膜EphA2表达显著下调；而外源性EphA2可促进滋养细胞侵袭，并激活MAPK通路和上调EMT指标。由此猜想：BPA可能通过母胎界面EphA2/ephrinA1介导反向信号转导影响滋养细胞EMT，最终导致胚胎着床异常。本项目拟利用人类临床资源、小鼠与细胞模型，在整体、细胞及分子水平探索环境水平BPA对母胎界面EphA2/ephrinA1表达及其对滋养细胞EMT的影响，为认识不良环境因素导致生殖健康受损的机制奠定基础。

Bisphenol A (BPA) is one of the most important environmental endocrine disruptors harmful to human reproductive health. Chronic exposure to BPA at environmental level is associated with decreased trophoblast invasion and embryo implantation rate, but the molecular mechanism is still unrevealed. Epithelial-mesenchymal transition (EMT) of trophoblast is one of the crucial processes of successful embryo implantation, which occurs not before embryo attachment. Therefore, cell-cell attachment might be essential to EMT, and Eph/ephrin family , which is expressed at the cell interface, is likely to play an important role in regulating embryo implantation. Our previous study indicated that the expression level of EphA2 significantly decreased in patients with higher urinary BPA concentration, and ectogenic EphA2 could increase trophoblast invasion with activating MAPK pathway and inducing EMT related molecules. Consequently, we hypothesized that BPA might interfere trophoblast EMT by EphA2/eprhinA1 reverse signaling pathway at the feto-maternal interface, and finally lead to implantation failure. In this research, using clinical materials, animal and cell-line models, we will investigate the effect of environmental BPA on EphA2/ephrinA1 expression at the feto-maternal interface and on the EMT of trophoblast. It is hoped that a better understanding of the pathogenesis of hazardous environmental factors on human reproductive health will provide us new insights on clinical therapy.