A Novel Molecule in Human Cyclic Endometrium: LncRNA TUNAR Is Involved in Embryo Implantation

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.

lincRNA RP24-315D19.10 promotes endometrial decidualization via upregulation of hnRNPA2B1

“…Several studies have shown that lncRNAs participate in the regulation of human disease pathogenesis through diverse mechanisms and serve as potential diagnostic and therapeutic targets (20,37). To date, several lncRNAs associated with endometrial decidualization have been identified, including TUNAR (38), HOXA11-AS(39), Hand2os1 (40), and PGK1P2 (41).…”

“…Several studies have shown that lncRNAs participate in the regulation of human disease pathogenesis through diverse mechanisms and serve as potential diagnostic and therapeutic targets (20, 37). To date, several lncRNAs associated with endometrial decidualization have been identified, including TUNAR(38), HOXA11-AS(39), Hand2os1(40), and PGK1P2(41). Studies have shown that these lncRNAs are abnormally expressed during endometrial decidualization in early pregnancy, implying that lncRNAs may play an important role in the development of endometrial decidualization.…”

The possible role of long non-coding RNAs in recurrent miscarriage

“…TUNAR (TCL1 Upstream Neural Differentiation-Associated RNA) is an approximately 1.0 kb lncRNA expressed explicitly in the human central nervous system and affects cell differentiation, proliferation, and apoptosis [ 69 , 70 ]. A study indicated that endometrial biopsies of the late proliferative phase were collected from patients with or without recurrent implantation failure, and the results showed luteinizing hormone (LH) levels of + 2 and + 7 [ 44 ]. Meanwhile, the TUNAR expression level in endometrium was downregulated in patients with LH levels of + 7 and upregulated in RM patients.…”

“…Meanwhile, the TUNAR expression level in endometrium was downregulated in patients with LH levels of + 7 and upregulated in RM patients. Multiple functions of TUNAR in endometrial epithelial cells (EECs) and endometrial stromal cells (ESCs) were investigated after transfection with pZW1-snoVector-TUNAR [ 44 ]. Wang et al [ 44 ] showed for the first time that lncRNA TUNAR was expressed in the human endometrium and might be implicated in embryo implantation by regulating attachment of blastocyst to the endometrial epithelium and modulating the decidualization and proliferation of ESCs.…”

Oviduct Transcriptomic Reveals the Regulation of mRNAs and lncRNAs Related to Goat Prolificacy in the Luteal Phase

“…LncGDAR was demonstrated to facilitate ovarian granulosa cell (GC) apoptosis by regulating the apoptosis-related genes in sheep [ 24 ]. LncRNA TUNAR may involve in embryo implantation by modulating the blastocyst attachment to the endometrial epithelium and regulating the proliferation and decidualization of ESCs [ 25 ]. Meanwhile, germ cell formation, early embryo implantation and development, and hormone regulation in human and animal reproduction are regulated by lncRNAs [ 18 , 26 ].…”