miRNA221/222介导人胚胎着床作用及调控机制研究

Embryo implantation is the critical step of reproductive process for many species. But the molecule mechanism of implatation and implantation disorder is still not identify, especially the molecule mechanism of human embryo implatation is knowed very few. It was confirmed that miRNA is the new target to regulate endometrium decidualization by preliminary research. On the basis of preliminary research and foreign research, miRNA221/222 possible reglate the embryo implantation by regulating the expression of p27. The project, combining togethergene array and bioinformatics model, apply human embryo implantation model in vitro, RNAi and luciferase report gene to verify the biological function, target gene and specificity target sequence of miRNA221/222 on human embryo implantation. The project start from miRNA to investigate the improtant physiology process of embryo implantation, and further to elucidate the molecular mechanism of embryo implantation disorder and habitual abortion to supply new theory basis and therapy strategy. The project provide new ideal and rationale of assisted reproductive technology on account of miRNA.

胚胎着床是许多物种生殖过程的关键步骤，但着床及着床障碍的分子机制尚不明确，特别人类胚胎着床的分子机制仍然知之甚少。前期工作已经证实miRNA是调控子宫内膜蜕膜化的新靶点，根据前期研究的基础和国内外研究提示miRNA221/222可能通过调控细胞因子p27的表达调控胚胎着床。本项目结合前期研究基础的基因芯片、生物信息学模型，拟采用体外人胚胎着床模型、RNAi技术和荧光酶报告基因等方法对miRNA221/222在人胚胎着床过程中确切的生物学功能、靶基因及特异性靶序列进行实验验证。本项目从miRNA新视角出发，探讨胚胎着床这一重要生理过程，将为进一步阐明胚胎着床障碍的分子机制及习惯性流产等相关疾病的病因学,提供新的理论依据，从而提供新的治疗策略，并为全新的基于miRNA的辅助生殖技术助孕方法提供新的思路和理论基础。

本课题以miRNA为视角，探讨ESC蜕膜化这一建立和维持妊娠的关键过程，通过体外胚胎着床模型进一步深入研究人胚胎在子宫内膜中着床过程，通过前期的实验结果和动物体内的相关研究发现在胚胎着床过程中miRNA222靶向调控p27，使其表达增高，与细胞周期蛋白E-CDK2和细胞周期蛋白D-CDK4结合抑制细胞周期进程，停滞在G1/S期，从而子宫内膜细胞蜕膜化，激活胚胎着床特异性基因的表达，为miRNA222通过p27调控子宫内膜蜕膜化，参与胚胎着床过程这一创新理论提供实验基础，将为进一步阐明胚胎着床障碍的分子机制及习惯性流产等相关疾病的病因学提供新的理论依据，从而提供新的治疗策略，并为全新的基于miRNA的辅助生殖技术助孕方法提供新的思路和理论基础。