子宫内膜容受性异常是导致反复胚胎种植失败（RIF）的主要原因，目前其建立的确切机制尚不清楚，且既往研究多关注蛋白编码基因的功能和机制研究，尚无长链非编码RNA在RIF子宫内膜容受性异常这一病理过程中的作用及机制报道。申请人前期研究发现lncARER1及其预测靶基因TIMP3在RIF患者着床期子宫内膜组织中表达显著上调，且过表达lncARER1促进基质细胞增殖和蜕膜化，同时显著上调TIMP3基因表达，提示lncARER1可能通过调控TIMP3基因及相关通路干扰子宫内膜容受性建立过程，影响胚胎植入，参与RIF发生。申请人拟在前期研究基础上，继续深入研究lncARER1对子宫内膜容受性建立过程的影响，阐明lncARER1调控TIMP3基因及相关通路的作用和机制，从而揭示lncARER1与RIF发生发展的相关性，为RIF表观遗传学病因研究提供线索。

Recurrent implantation failure (RIF) is a condition in which infertile couples fail to achieve a clinical pregnancy following repeated transfers with high quality embryos during in vitro fertilization (IVF). Although the underlying pathogenesis of RIF remains poorly characterized, it is increasingly apparent that this heterogeneous disease is coupled to aberrant endometrial receptivity. To date, accumulated evidence has underlined the importance of the protein-encoding genes in a functioning and receptive endometrium. However, the regulation mechanism of distorted endometrial receptivity in RIF has been remained enigmatic. Therefore, it is necessary to explore the pathogenesis of endometrial dysfunction in RIF from other viewpoints. Our previous researches exhibited that long non-coding RNA (lncRNA) lncARER1 and its predicted target gene TIMP3 were elevated in endometrial tissues from RIF patients. Forced expression of lncARER1 significantly promoted human endometrial stromal cells proliferation and decidualization. Meanwhile, lncARER1 overexpression markedly up-regulated the expression of TIMP3 gene in stromal cells. It is presumed that dysregulated lncARER1 may be responsible for abnormal endometrial receptivity and subsequent implantation failure in RIF via disordering TIMP3 gene and its related signalling pathway. Based on the previous results, we will investigate the influence of lncARER1 in endometrial receptivity and further reveal the underlying mechanism of lncARER1 by regulating TIMP3 and its related signalling pathway in RIF. Our findings will provide new insights into epigenetic pathogenesis in aberrant endometrial receptivity for RIF and strengthen the concept that modulating disordered lncRNAs might make for bettering endometrial receptivity and implantation rates in RIF patients.