ENPP3促进子宫内膜容受性的分子机制研究

The adequate endometrial receptivity is of great significance in successful embryo implantation. Despite our increased understanding of the cytokines related with the receptive endometrium, there has no marker been successfully converted into clinical practice. Ectonucleotide pyrophosphatase–phosphodiesterase 3 (ENPP3), a protein that was reported to promote the invasion of tumor cells, which has parallels with the process of embryo implantation. Previously, our research group has found that progesterone regulated ENPP3 was expressed in human endometrial epithelial cells and its expression levels changed during the menstrual cycle, peaking in the mid-secretory phase, corresponding to the time of embryo implantation. In addition, it has found that the expression of ENPP3 in uterine fluid was correlated to that in the endometrium. On the basis of the previous finding, we will go further to analyse the level of ENPP3 in uterine fluid on the window of peri-implantation of women with a history of recurrent implantation failure(RIF) by enlarging the sample size, to determine its roles in endometrial receptivity and its corresponding molecular mechanism, and to provide a non-invasive test of endometrial receptivity for RIF patients.

良好的子宫内膜容受性是胚胎成功着床的关键步骤。已经有多种细胞因子被发现与子宫内膜容受性相关，但至今没有单个标记物能成功地转化用于临床。ENPP3能促进肿瘤侵袭，我们前期研究发现ENPP3表达于人子宫内膜上皮细胞，其在子宫内膜分泌中期表达量显著增加，并受孕激素调控，此外，研究发现宫腔液中ENPP3的表达与子宫内膜组织中具有一致性。本项目将在前期工作的基础上，首先增加样本量，观察反复种植失败患者与正常妇女种植窗宫腔液中ENPP3的表达差异，继而通过构建胚胎黏附和侵袭模型确定ENPP3对胚胎着床的作用；并进一步通过表达谱芯片寻找ENPP3促进胚胎着床相关的信号通路，最终通过一系列的分子生物实验阐明ENPP3促进子宫内膜容受性的分子机制，为反复种植失败患者提供评估内膜容受性的方法，从而指导临床。

良好的子宫内膜容受性是胚胎成功着床的关键步骤。已发现多种细胞因子与子宫内膜容受性相关，但至今没有单个标记物能成功地转化用于临床。我们的研究发现ENPP3表达于人子宫内膜上皮细胞，其在子宫内膜分泌中期表达量显著增加，并受孕激素调控，此外，研究发现宫腔液中ENPP3的表达与子宫内膜组织中具有一致性。本项目在前期工作的基础上，通过增加样本量，阐明ENPP3在子宫内膜细胞中的表达和分布，证实ENPP3受孕激素调控并能促进胚胎黏附和侵袭，阐明ENPP3通过促进integrin β3的表达影响胚胎种植。另外，我们发现ENPP3在反复种植失败患者子宫内膜上表达明显降低，可将其作为评估反复种植失败患者子宫内膜容受性的分子标志物，从而指导临床。