The effect of letrozole and calcitriol on the expression of uterine receptivity genes in 3D culture of endometrial tissue of Repeated Implantation Failure patients and healthy women

Abstract

Determining the exact time of window of implantation (WOI) in individuals with 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 PCR. Results: This study showed that the expression level of pre-implantation genes (NR3C1, LIF HOXA10, miR-30d, HOXA11, Integrin αv, Integrin β3) in RIF patients was lower than healthy women and the expression level of anti-implantation genes (BCL6, miR- 145, miR-23b and miR-494) were higher in RIF patients than healthy women. In all three types of treatment (letrozole, calcitriol and co-treatment with letrozole and calcitriol), the expression level of pro-implantation genes (HOXA10, HOXA11, Integrin αv, NR3C1, miR-30d) increased except for LIF and Integrin β3 in RIF patients and healthy women. In addition, in all three types of treatment (letrozole, calcitriol and co-treatment with letrozole and calcitriol), the expression level of anti-implantation genes (miR-145, miR-23b, miR-494 and BCL6) in RIF patients and healthy women decreased.