Abstract
Embryo implantation rate remains an inefficient process in in vitro fertilization and embryo transfer (IVF-ET) cycles. The role long non-coding RNA (lncRNA) plays in embryo implantation remains unclear. We aimed to investigate the expression pattern of lncRNA TCL1 upstream neural differentiation-associated RNA (TUNAR) in human cyclic endometrium and clarify the role of TUNAR in the development of endometrial receptivity. Endometrial biopsies were collected at the late proliferative phase, luteinizing hormone (LH) + 2 and LH + 7, from patients with or without recurrent implantation failure (RIF). Real-time RT PCR was performed to detect the level of lncRNAs. After pZW1-snoVector-TUNAR transfection, multiple function of TUNAR in endometrial epithelial cells (EECs) and endometrial stromal cells (ESCs) was investigated. The expression of TUNAR in endometrium was found down-regulated at LH + 7 and up-regulated in RIF patients. In proliferative phase, TUNAR was overwhelmingly more abundant in ESCs and regulated its proliferation. In LH + 7, the difference in the expression of TUNAR between ESCs and EECs was narrowed. Overexpression of TUNAR not only impaired spheroid attachment to EECs, but also inhibited decidualization of ESCs. TUNAR was found expressed in human endometrium for the first time, which might be involved in embryo implantation by modulating the blastocyst attachment to the endometrial epithelium and regulating the proliferation and decidualization of ESCs. Our study helps us to better understand the molecular mechanisms of embryo implantation and may provide a promising biomarker of endometrial receptivity.
Highlights
Despite the technical advances that have continued to evolve in the area of assisted reproduction, overall pregnancy and implantation rates have remained relatively low
These results are consistent with our previous RNA sequencing (RNA-seq) data (Supplementary Table 2), suggesting that these eight long non-coding RNA (lncRNA) might be involved in endometrial receptivity
We demonstrated that TCL1 upstream neural differentiation-associated RNA (TUNAR) is expressed in human cyclic endometrium with its expression levels increased at luteinizing hormone (LH) + 2 and decreased at LH + 7
Summary
Despite the technical advances that have continued to evolve in the area of assisted reproduction, overall pregnancy and implantation rates have remained relatively low. It is clear that the success of in vitro fertilization and embryo transfer (IVF-ET) cycles depends upon embryo quality and on uterine receptivity as the transfer of euploid embryos following preimplantation genetic testing for aneuploidies (PGT-A) still does not guarantee implantation (De Rycke et al, 2015). The process of implantation in the uterus results from a complex set of events as a result of highly orchestrated “cross talk” between a euploid blastocyst and a receptive endometrium These occur through a series of coordinated genetic and hormonal events regulating intracellular signaling in LncRNA TUNAR and Embryo Implantation both the host uterus and implanting blastocyst (Dominguez et al, 2002). When this cross talk fails to occur repeatedly, this phenomenon is referred to as recurrent implantation failure (RIF) in spite of the transfer of normal appearing embryos fails to lead to the stage of recognizable intrauterine sac (Coughlan et al, 2014)
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