Upregulated RPA2 in endometrial tissues of repeated implantation failure patients impairs the endometrial decidualization

Abstract

Purpose: To investigate the expression and underlying mechanism of RPA2 in endometrium of patients with repeated implantation failure (RIF).

Methods: In this study, we retrieved the expression profiles from GEO databases and filtered the differentially expressed genes between RIF and the fertile control group. Ultimately, RPA2 was confirmed as a target gene. RPA2 expression in endometrial tissues of RIF patients, the control group, and different phases was detected by RT-qPCR, immunohistochemistry, and Western blotting. The role of RPA2 in endometrial decidualization was performed by in vitro decidualization inducing by 8-Br-cAMP and MPA. Furthermore, RT-qPCR was used to detect changes in the decidual biomarkers after transfection of RPA2 overexpression vector in human endometrium stromal cell (HESC).

Results: RPA2 was significantly upregulated in the mid-secretory endometrium of patients with RIF. As a proliferation-related gene, RPA2 was obviously higher expressed at proliferative phase during the normal menstrual cycles. Moreover, the downregulation of RPA2 was discovered during decidualization of HESC. Furthermore, RPA2 overexpression impaired decidualization by inhibiting the expression of prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1).

Conclusions: Our finding indicated that aberrant upregulation of RPA2 attenuated decidualization of HESC in RIF women and provided new potential therapeutic targets.

Keywords: Decidualization; Human endometrial stromal cell (HESC); RPA2; Repeated implantation failure (RIF).