长链非编码RNA- TUNAR和LINC01502在子宫内膜容受性建立中的作用及其机制

Compatible endometrial receptivity is essential for successful implantation.The underlying molecular mechanisms are continuously focused in assisted reproduction field with the protein-encoding genes and miRNAs. However, the effects and regulatory mechanims of long non-coding RNAs (lncRNAs) on endometrial receptivity are poorly understood. By using RNA-Seq technology,our recent study have identifed two lncRNAs- TUNAR and LINC01502, which undego the most dramatic changes in the pre-receptive and receptive endometrium. Both of them were found to play key roles in implantation as demonstrated by an in vitro implantation model. In this project, we will examine the mechanisms of TUNAR and LINC01502 in endometrial receptivity and implantation by using cultured primary endometrial epithelian cells, in vitro implantation and animal model. RNA pull down, RIP-qPCR and ChIRP-Seq will be applied to clarify the regulatory mechanisms underlying these functions of TUNAR and LINC01502. It is conceivable that sucessful carry out of this proposed novel study of lncRNAs would help for better understanding the molecular mechanisms that control endometrial receptivity, which may implicate in the understanding of the pathogenesis of repeated implantation failure and in improving implantation rate in IVF-ET.

子宫内膜容受性是影响胚胎着床的关键因素，因此其建立机制和影响因素成为目前辅助生殖领域的研究热点。蛋白编码基因及miRNA对子宫内膜容受性的调控机制已被广泛研究，但长链非编码RNA对子宫内膜容受性的调控机制还鲜有报道。申请人前期利用RNA-Seq筛选到着床前期和着床期人子宫内膜差异表达最显著的两个长链非编码RNA-TUNAR和LINC01502，利用体外种植模型进一步研究发现，它们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，体外种植模型及小鼠动物模型解析TUNAR和LINC01502在子宫内膜容受性建立及胚胎着床中的具体功能，并利用RNA pull down, RIP-qPCR和ChIRP-Seq等方法阐明其作用机制。本研究将从不同于蛋白编码基因的角度诠释子宫内膜容受性建立的分子机制，对防治反复种植失败、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着床的关键因素，其建立机制和影响因素已成为目前辅助生殖领域的研究热点。本课题组围绕子宫内膜容受性开展了一系列基础和临床研究，在前期RNA-Seq高通量测序结果的基础上，通过细胞生物学、分子生物学和系统生物学多角度多层次的综合研究，阐明了lncRNA-TUNAR在子宫内膜容受性建立和胚胎着床中的功能及分子机制，揭示了多囊卵巢综合征患者子宫内膜容受性缺陷的致病因素和分子机制。通过子宫内膜容受性相关临床研究，明确了IVF-ET中三维超声对子宫内膜容受性评估价值。通过国内多中心大型RCT研究，为优化临床胚胎移植策略提供循证医学A级证据，有助于提升IVF临床妊娠率。既从基础理论上加深了对子宫内膜容受性建立过程中的调控网络的理解，还筛选出新的内膜容受性的标志分子，同时为临床反复种植失败患者的诊断和治疗提供潜在的靶点。