细胞外基质胶原受体DDR2影响黄体血管新生的作用及机制研究

卵巢血管异常性不孕症发病率高达5%-8%。血管新生是黄体生成中的关键事件，除激素外，细胞外基质构成的微环境对血管新生也起重要调控作用。胶原盘状结构域受体2（Discoidin domain receptor 2 ，DDR2）在卵巢的表达呈周期性变化，黄体早期达最高；Ddr2-/-小鼠在促性腺激素及卵泡储备均正常的情况下不孕、并黄体生成障碍，但机制不祥。我们研究发现，Ddr2-/-小鼠黄体早期血管密度及功能均显著低于WT，推测其可能是血管新生障碍导致黄体功能不全的外周性不孕。本项目拟利用Ddr2-/-小鼠、小分子抑制剂等通过功能学、形态学、细胞生物学及分子生物学方法，深入研究DDR2参与黄体血管新生影响卵巢功能的作用及机制，并阐明DDR2调控HIF-1α影响血管内皮细胞增殖及黄体细胞VEGF分泌的分子机制，对卵巢细胞外基质的作用提出新认识，为血管异常性不孕的诊断治疗及避孕药的研发提供新靶点。

The Incidence of infertility caused by Ovarian vascular abnormalities as high as 5%-8%，Periodic angiogenesis play an pivotal role for the function of ovary。In addition to the hormone, the microenvironment composed by extracellular matrix in ovarian also play an important regulatory role for angiogenesis。Discoidin domain receptor 2（DDR2）is a fibrillar collagen receptor, widely expressed in ovary interstitial and have a cyclic variation，reaches the highest at luteal phase. the Ddr2-/-mice are infertile while the gonadotropin and follicle reserve normal, have disorder of luteinization. Our research found that DDR2 involved in angiogenesis，the vascular density and penetration in Ddr2-/- mice ovary is significantly lower than WT mice at Luteal phase,We hypothesized that the reason of Ddr2-/- mice infertility is corpus luteum dysfunction caused by angiogenesis obstacles. This project intends to Study the effect and mechanism of DDR2 participation in ovulation and luteinization by using Ddr2-/-mice and various research methods such as morphology, cytology and molecular biology methods，to investigate the molecular mechanisms of DDR2 involved in Luteal angiogenesis, to provide a new targe for contraception research and treatment of infertility caused by Ovarian vascular abnormalities.