胚胎着床是妊娠建立的关键步骤。在妊娠损失中，75%是由着床失败导致的。已知在小鼠子宫腔中注射油滴或者搔刮等机械刺激可引起蜕膜化反应。在卵巢刺激的前一个周期，对人子宫内膜进行局部损伤，有助于提高妊娠率，但其机理一直不清楚。最近研究表明，人角膜及支气管上皮等受到机械损伤等刺激后可释放大量的ATP，这些ATP可激活COX-2、Egr1、p-Stat3及cPLA2等胚胎着床相关分子。我们的前期结果证实着床期胚胎及子宫腔中含有高水平的ATP，推测胚胎或受损子宫上皮释放的ATP可能在胚胎着床及蜕膜化中起重要作用。我们拟以小鼠体内及体外模型以及人子宫内膜细胞系为材料，通过机械损伤、升高或降低ATP浓度及ATP受体抑制剂处理等手段，分析ATP与子宫接受性、蜕膜化、肌肉收缩以及上皮-基质对话等关系，明确胚胎或受损子宫上皮释放的ATP在胚胎着床及蜕膜化中的调节与功能。本项目将有助于了解胚胎着床和蜕膜化的机理。

Embryo implantation is a key step for establishing pregnancy. Among the pregnancy loss, 75% is caused by implantation failure. It is known that decidual reaction can be induced by oil injection or mechanical stretch of uterine lumen. For assisted reproduction, local endometrial injury during the previous cycle is beneficial for increasing pregnancy rate. However, the underlying mechanism is still not clear. Recent data suggest that human corneal or tracheal epithelium can release a large amount of ATP under the stimulation of mechanical damage, stretch or inflammation. The released ATP can activate many implantation-related genes, including COX-2, Egr1, p-Stat3 and cPLA2. Our preliminary data also showed that there is a high level of ATP in preimplantation blastocysts and uterine fluid. We assume that ATP released from blastocyst or damaged uterine epithelium may play a key role during embryo implantation and decidualization. We will use mouse models in vivo and in vitro, and human endometrial cell lines to analyze the effects of ATP on uterine receptivity, decidualization, muscular contraction and epithelium-stromal interaction. This study will characterize the regulation and function of released ATP from embryos and damaged uterine epithelium during embryo implantation and decidualization. Data from this study will shed lights on understanding the mechanism of embryo implantation and decidualization.