环状RNA- hsa_circRNA_101280对子宫内膜容受性的作用机制

Compatible endometrial receptivity is essential for successful implantation. The underlying molecular mechanisms are the focus in assisted reproduction field. While the effects of protein-encoding genes, miRNAs and lncRNAs have been extensively addressed, the effects and regulatory mechanisms of circular RNAs on endometrial receptivity have never been addressed. By using circRNA microarray, our recent study have identified one circRNA- hsa_circRNA_101280, which is highly expressed in the receptive endometrium. It was found that hsa_circRNA_101280 played a key role in implantation in an in vitro implantation model. However, the exact effects of hsa_circRNA_101280 in endometrial receptivity and implantation await to be investigated. In this project, we will examine the effects and the underlying mechanisms of hsa_circRNA_101280 in endometrial receptivity and implantation by using cultured primary endometrial epithelial cells and an in vitro implantation model. The miRNA sponge and interacting proteins will be studied to clarify the underlying regulatory mechanisms. We believe that successful carry out of this project may shed new light on the molecular mechanisms that control endometrial receptivity, and may reveal a new target for the diagnosis and treatment of repeated implantation failure, which is of great significance in the improvement of the IVF-ET embryo implantation rate.

子宫内膜容受性是决定胚胎能否顺利着床的关键因素，其建立机制和影响因素是目前辅助生殖领域的重要研究方向。内膜容受性关键调控分子的研究目前主要集中在某些蛋白编码基因、miRNA以及lncRNA分子上，而环状RNA对子宫内膜容受性的调控机制还未见任何报道。申请人前期利用环状RNA microarray筛选到着床期人子宫内膜显著性高表达的环状RNA-hsa_circRNA_101280，利用体外种植模型进行的初步研究表明其在胚胎着床中起着重要作用，但具体功能尚不清楚。本项目拟利用原代培养的子宫内膜细胞及体外种植模型解析hsa_circRNA_101280在子宫内膜容受性建立及胚胎着床中的具体功能，并从miRNA海绵和相互作用蛋白两个角度阐明其作用机制。本研究将为阐明子宫内膜容受性建立的分子机制开拓新的方向、为反复种植失败的诊疗提供新的靶点，对提高IVF-ET胚胎种植率具有重要意义。

子宫内膜容受性是影响胚胎植入的关键因素，其建立机制和影响因素是目前辅助生殖领域的研究热点。本项目主要是围绕子宫内膜容受性开展一系列基础与临床研究。首先通过组学、体外细胞模型及模式动物等研究手段，阐明了环状RNA has-circRNA-101280及长链非编码 lncRNA-TUNAR在子宫内膜容受性建立和胚胎植入中的作用及机制。其次通过筛选及鉴定前期组学筛选的内膜容受性关键分子，利用已建立子宫内膜临床生物样本库，揭示了表观遗传及代谢异常在反复种植失败相关疾病中的作用机制，为临床胚胎移植策略的选择提供证据。这些研究成果即从理论上加深了子宫内膜容受性建立过程中的分子调控网络的理解，同时筛选出新的子宫内膜容受性生物标志物，为反复种植失败患者提供潜在的诊疗靶点。在本项目的资助下，共发表论文18篇，其中SCI论文16篇，申请专利2项，培养研究生5名。项目负责人作为第一完成人获得上海医学科技奖一等奖及第六届“中国女医师协会五洲女子科技奖”临床医学科研创新奖等奖励。