Genes & diseasesOct 27, 2025

Loss of vitamin D receptor may increase uterine lining scarring through cell recycling changes

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 7, 2026

Abstract

VDR protein expression was lower in the endometria of patients with intrauterine adhesion (IUA) compared to controls.

Silencing the vitamin D receptor (VDR) in endometrial cells inhibited the process of cellular recycling (autophagy) and increased markers associated with tissue transition (epithelial-mesenchymal transition).
Overexpression of VDR reduced the activation of key signaling pathways (p-MTOR, p-AKT, p-MAPK/ERK) involved in cell growth and survival.
In VDR knockout mice, endometrial tissue showed signs of fibrosis and changes in the expression of proteins related to cellular recycling and tissue transition.
Treatment with rapamycin was able to reverse the effects observed in VDR knockout mice, suggesting potential therapeutic avenues.

Simplified

Intrauterine adhesion (IUA) leads to infertility or recurrent abortion; however, its etiology and pathological mechanism remain unclear. To explore the role and mechanism of the vitamin D receptor (VDR) in the pathogenesis of IUA. We found that VDR protein expression was lower in the endometria of patients with IUA than in those of the control group. Silencing VDR in endometrial epithelial cells inhibited autophagy, promoted the epithelial-mesenchymal transition (EMT) overexpression, and increased the phosphorylation of p-MTOR, p-AKT, and p-MAPK/ERK, while its overexpression suppressed the phosphorylation of p-MTOR, p-AKT, and p-MAPK/ERK. Also, the interaction between the VDR and p62 proteins was detected. Endometrial tissue in VDR knockout mice exhibited fibrosis, reduced VDR expression, decreased ATG7, LAMP1, and LC3-II levels, and increased p62 expression; the expression of the EMT marker CDH1 decreased while that of CDH2 increased. Treatment with rapamycin reversed this process. Our data indicate that the VDR receptor is a potential marker for diagnosing and treating IUA and that vitamin D may serve as a therapeutic agent for IUA.

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The authors declare that they have no competing interests.

PubMed

Loss of vitamin D receptor may increase uterine lining scarring through cell recycling changes

Abstract

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