Progesterone receptor, prokineticin 1, LncRNA-H19, and miR-210 in molecular regulation of recurrent implantation failure

Abstract

Abstract Recurrent implantation failure (RIF) is a major challenge in reproductive medicine. This study explores the expression profiles and interactions of progesterone receptor B (PGR-B), prokineticin 1 (PROK1), prokineticin receptor 1 (PROKR1), and their regulatory associations with microRNA-210-5p (miR-210-5p) and long non-coding RNA H19 (lncRNA-H19) within endometrial tissue. This case-control study was conducted from June 2021 to July 2023, involving 50 patients with recurrent implantation failure (RIF) and a control group of 50 women with successful term pregnancies. Participants were recruited from Arash Hospital in Tehran, Iran. Hysteroscopic assessments were done for the RIF group, while the control group had sampling via Pipelle catheter. We measured the expression levels of key molecular markers, including PGR-B, PROK1, PROKR1, lncRNA-H19, and miR-210-5p, using quantitative real-time PCR (qRT-PCR). Our findings demonstrate significantly low expression and protein levels of PGR-B and PROK1, suggesting a potential dysregulation of these biomolecules in the studied context. Notably, we observed a strong positive correlation between PGR-B and PROKR1, suggesting a synergistic regulatory relationship, potentially influencing endometrial signaling pathways. Conversely, in fertile women, PGR-B and PROK1 exhibited a positive correlation with miR-210-5p, implicating miR-210-5p as a potential activator of PGR-B downstream pathways. Additionally, a positive correlation between PGR-B and PROK1 with lncRNA-H19 was identified, hinting at a complex regulatory network involving these non-coding RNAs. Our findings indicated that a regulatory network involving PGR‑B, PROK1, PROKR1, lncRNA‑H19, and miR‑210‑5p in women with RIF. The significant correlation between these molecules underscores the importance of angiogenesis, a novel mechanistic link to impaired decidualization and endometrial receptivity. It provides new insight into the molecular basis of implantation failure.