LncRNA NEAT1 affects endometrial receptivity by regulating HOXA10 promoter activity

Abstract

ABSTRACT In vitro fertilization and embryo transfer (IVF-ET) is one of the effective methods to treat female infertility. Poor endometrial receptivity (ER) is an important factor leading to embryo implantation dysfunction, which can reduce pregnancy rate of IVF-ET. The mice model with embryo implantation dysfunction in vivo and attachment model of trophoblast (JAR) spheroids in vitro were constructed. The levels of lncRNA NEAT1, HOXA10, CTCF and markers of ER were detected. The cell proliferation was measured. The interaction between lncRNA NEAT1 and CTCF, HOXA10 promoter and CTCF were confirmed. LncRNA NEAT1 and HOXA10 levels in infertile patients and mice model with embryo implantation dysfunction were increased. In vitro experiments showed that down-regulation of lncRNA NEAT1 improved EECs proliferation and ER marker expressions. LncRNA NEAT1 could bind to CTCF, and CTCF could bind to HOXA10 promoter and down-regulate HOXA10 gene expression by regulating histone modification level. The lncRNA NEAT1/CTCF/HOXA10 signaling pathway regulated EECs proliferation and ER establishment in vitro and in vivo. Our study suggested that lncRNA NEAT1 could up-regulate HOXA10 promoter activity and its expression by combining with CTCF, thus improving EECs proliferation and ER establishment, and ultimately facilitating embryo implantation.