CXCL12/CXCR4/CXCR7在子宫内膜容受性形成中的作用

The establishment of endometrial receptivity and crosstalk between trophoblast and endometrium are two crucial steps for embryo implantation. Our previous researches (No.30801240) have shown that CXCL12/CXCR4 axis is involved in not only first-trimester trophoblast proliferation and invasion, but also decidual stromal cell migration and motility. Recent immunocytochemistry analysis also confirms the expression of CXCR7, the second receptor for CXCL12, in human first-trimester trophoblasts and decidual stromal cells. These results indicate the important role of CXCL12/CXCR4/CXCR7 axis in the interaction of various types of cells at the materno-fetal interface. The present study explores the expression of CXCL12/CXCR4/CXCR7 in human endometrium during menstrual cycles and compares the difference of CXCL12/CXCR4/CXCR7 expression pattern between normal and infertile women. The modulation by CXCL12/CXCR4/CXCR7 in the biological function of epithelial cells and stromal cells, the two mian components of human endometrium, is also investigated via an in vitro decidualization model. We aims to elucidate the role of CXCL12/CXCR4/CXCR7 axis in the establishment of endometrial receptivity, which is constructive to understand the mechanisms of implantation and shade some lights on the clinical diagnosis and treatment for infertility.

着床期子宫内膜容受性建立及其与滋养细胞的精细对话是胚胎成功植入的关键因素。前一项研究（No.30801240）发现，CXCL12/CXCR4信号通路不仅调节早孕期滋养细胞增殖与侵袭，还促进蜕膜基质细胞迁移与运动；近期研究发现滋养细胞和蜕膜基质细胞表达CXCL12的第二受体CXCR7。提示CXCL12/CXCR7/CXCR4是介导母-胎界面各种细胞相互作用的重要桥梁。因此本课题拟分析CXCL12/CXCR4/CXCR7在正常人月经周期不同时段子宫内膜的表达模式；比较它们在正常生育史妇女和不孕症患者着床期子宫内膜的表达区别；并建立体外细胞培养模型，解析它们对着床期子宫内膜腺上皮细胞和基质细胞的生物学调节作用及分子机制。通过解析CXCL12/CXCR4/CXCR7在着床期子宫内膜的表达规律和生物学作用揭示子宫内膜容受性建立的分子机理，为探寻不孕症的发病机制、临床诊断及治疗提供科学依据。

着床期子宫内膜容受性的建立及其与滋养细胞的精细对话是胚胎成功植入的关键因素。本课题在前期研究基础上，利用real-time PCR、免疫细胞化学、免疫组织化学、Western blot、ELISA等技术，在基因水平和蛋白水平，分析了CXCL12/CXCR4/CXCR7在正常人月经周期不同时段子宫内膜的表达模式；并着重分析了CXCL12/CXCR4/CXCR7在子宫内膜重要功能细胞：子宫内膜间质细胞及子宫内膜腺上皮细胞的表达情况；同时还采用体外原代细胞培养，解析了CXCL12/CXCR4/CXCR7信号通路对子宫内膜间质细胞和子宫内膜腺上皮细胞的生物学调节作用，及其与滋养细胞的相互调控机制。我们的研究提示，CXCL12/CXCR4/CXCR7可能是介导胎儿来源的滋养细胞与母体细胞（包括子宫内膜间质细胞和子宫内膜腺上皮细胞两种重要功能细胞）相互作用的重要分子。我们的研究结果有助于揭示子宫内膜容受性建立的分子机理和母-胎免疫调节机理，对探寻不孕症的发病机制及临床治疗也有积极意义。