Study of LIF, NR3C1, BCL6, miR-494, and miR-30d in Endometrial Epithelial Cells of Repeated Implantation Failure and Healthy Women Treated with Calcitriol and Letrozole in a Fibrin Scaffold

Abstract

Background: Determining the exact time of window of implantation (WOI) in individuals with repeated implantation failure (RIF) is necessary for successful implantation. The present study aimed to compare the effects of letrozole and/or calcitriol on the expression of receptivity markers in endometrial epithelial cells (EECs) of RIF patients and healthy fertile women. Methods: Endometrial tissue was obtained from RIF patients (n=5) and healthy women (n=5) in the proliferation phase. EECs were isolated and cultured in a fibrin scaffold in 10 groups. The cells were treated with letrozole and/or calcitriol in three types of treatment. To check the proliferation and migration of cells in the scaffold, immunofluorescent and H&E staining was used, and gene expression was checked using real-time polymerase chain reaction (PCR). Results: This study showed that the expression levels of pro-implantation genes (NR3C1, LIF, and miR-30d) were higher in healthy women than in RIF patients, and the expression levels of anti-implantation genes (BCL6 and miR-494) were lower in healthy women than in RIF patients. Calcitriol and letrozole increased the expression level of pro-implantation genes (NR3C1, LIF, and miR-30d) in RIF patients. Furthermore, they reduced the expression level of anti-implantation genes (BCL6 and miR-494) in RIF patients. Conclusion: Our findings suggest that treatment with letrozole is more effective than co-treatment with letrozole and calcitriol or alone treatment with calcitriol on receptivity markers in RIF patients.