# Unveiling the Role of Vitamin D/VDR in Promoting Endometrial Decidualization

## TL;DR

This study shows that vitamin D promotes endometrial cell changes needed for pregnancy, likely through its receptor and estrogen signaling.

## Contribution

The novel finding is that vitamin D and VDR directly regulate decidualization markers and estrogen signaling in endometrial cells.

## Key findings

- Vitamin D increases decidualization markers PRL and IGFBP1 in a dose- and time-dependent manner.
- VDR knockdown reduces decidualization markers, while VDR overexpression enhances them.
- VDR binds directly to the promoters of CYP19 and ESR1, linking vitamin D to estrogen signaling.

## Abstract

Vitamin D’s impact on reproductive health, particularly endometrial receptivity, has attracted significant attention. This study investigated the effects of vitamin D and its receptor (VDR) on decidualization in human endometrial stromal cells (HESCs). An in vitro decidualization model was established by culturing immortalized T‐HESC or primary HESC in differentiation medium, treated with different concentrations of 1,25(OH)2D. VDR expression was modulated using siRNA, and cell morphology was analyzed by immunofluorescence. Decidualization markers (PRL and IGFBP1), vitamin D metabolic enzymes (CYP27B1 and CYP24A1), and VDR were measured using Western blot, qPCR, and ELISA. Aromatase (CYP19), estrogen receptor (ESR1), and estradiol (E2) expressions were also assessed. Cell proliferation was evaluated using the CCK‐8 method. During T‐HESC decidualization, CYP27B1 expression significantly increased by Day 4, peaking on Day 8, whereas VDR expression increased progressively, and CYP24A1 levels remained stable. A high concentration of vitamin D significantly upregulated PRL and IGFBP1 transcription, increased CYP19 and VDR expression, elevated E2 and PRL secretion, and promoted ESC proliferation. VDR knockdown inhibited ESC decidualization, reducing PRL, IGFBP1, ESR1, and CYP19 expression, whereas VDR overexpression enhanced these markers. ChIP‐qPCR analysis demonstrated that VDR directly binds to the promoter regions of CYP19 and ESR1 in HESC. Vitamin D treatment significantly upregulated the expression of PRL, IGFBP1, CYP27B1, VDR, CYP19, and ESR1 in primary HESC on Day 8 of decidualization. These findings suggest that vitamin D promotes ESC decidualization in a dose‐ and time‐dependent manner via a VDR‐mediated mechanism, with estrogen signaling potentially playing a key role.