The long noncoding RNA PTENP1 regulates human endometrial epithelial adhesive capacity in vitro: implications in infertility

Abstract

There is general consensus that the synchronous development of the embryo and endometrium is absolutely essential for successful implantation. Recent studies have strongly suggested that embryo-secreted factors are able to deliver into the endometrial cavity/endometrium and alter its protein profile in preparation for implantation. However, there is limited research focusing on long noncoding RNA (lncRNA) changes in the endometrium that brought about by the embryonic derived factors. It has been suggested that lncRNA has intricate interplay with microRNA (miR), small (~19-22 nucleotides), non-protein-coding RNA, to regulate protein production in the endometrium, thus controlling adhesive capacity. Here through microarray assays, we compare the lncRNA profile of the primary human endometrial epithelial cells (HEECs) that have been precultured with blastocyst-conditioned media (BCM) from embryos that implanted versus nonimplanted. Our data indicate a substantial change of lncRNA expression in HEECs, including 9 up-regulated and 12 down-regulated lncRNAs after incubation with implanted BCM. Selective knockdown of PTENP1, the most increased lncRNA after implanted BCM treatment in the HEECs, compromised the spheroid adhesion (P < 0.001). Characterization of PTENP1 confirmed its expression in the luminal epithelium with staining appeared most intense in the midsecretory phase. Furthermore, we have recorded a substantial change of miR profile upon PTENP1 knockdown in HEECs. Overexpression of miR-590-3p, a novel predicted target of PTENP1, impaired spheroid adhesion (P < 0.001). Collectively, these data have supported a novel regulation system that lncRNAs were able to participate in the regulation of implantation through association with miRs.

Keywords: PTENP1; endometrium; human reproduction; implantation; long noncoding RNA; miR-590-3p; microRNA.