Endometrial Vitamin D Receptor Expression by mRNA and Immunohistochemistry in Women with Recurrent Implantation Failure and Unexplained Infertility

Abstract

Background Although not a major determinant of receptivity, underexpression of the vitamin D receptor (VDR) is associated with endometrial dysfunction. This study aimed to determine VDR expression in the endometrium of patients with recurrent implantation failure (RIF) and unexplained infertility (UEI) using polymerase chain reaction (PCR) and immunohistochemistry. Methods A total of 75 patients (25 RIF, 25 UEI, and 25 fertile controls) were enrolled in the study. In the control group, only patients with early luteal phase histology according to Noyes' criteria were included to match the endometrial sampling timing of the RIF and UEI groups; patients with follicular and mid-luteal phase histology were excluded, and enrollment continued until 25 eligible patients were identified. Serum vitamin D (VD) levels were measured in all participants. Endometrial tissue was collected using a Pipelle cannula at the time of oocyte retrieval. VDR transcript variant 2 (VDR2) and 4 (VDR4) expression was analyzed using PCR. Endometrial tissue was subjected to VDR immunostaining. Results VDR2 expression in the RIF group (0.37 +/- 0.02 vs. 1.01 +/- 0.03, p < 0.001) and UEI group (0.28 +/- 0.01 vs. 1.01 +/- 0.03, p < 0.001) was significantly lower compared to the control group. VDR2 expression was similar in the RIF and UEI groups. VDR4 expression in the RIF group (0.46 +/- 0.02) was significantly lower than that in the UEI (1.16 +/- 0.07) and control (1.02 +/- 0.05) groups (p < 0.001 for each comparison). VDR4 expression in the UEI and control groups was similar. The histo-score values of the RIF (0.49 +/- 0.03) and UEI (0.35 +/- 0.03) groups were significantly lower than those of the control group (1.24 +/- 0.13) (p < 0.001 for both). In the RIF group, VDR2 was positively correlated with VD (r = 0.593, p = 0.002) and endometrial thickness (r = 0.627, p < 0.001). Conclusion Low serum vitamin D levels in patients with RIF and UEI were found concomitantly with low VDR expression in the endometrium. Further research is needed to determine whether VD supplementation and adjustment of serum VD concentrations modulate VDR expression and its effects on embryo implantation.