Advances in the Pathophysiology of Thin Endometrium.

Authors

Yifei Niu, Aiwen Le

Published in

Reproductive sciences (Thousand Oaks, Calif.). May 30, 2025. Epub May 30, 2025.

Abstract

A thin endometrial lining, typically defined as an endometrial thickness of less than 7 mm, is commonly associated with failed embryo implantation, recurrent pregnancy loss, and infertility. This review summarizes the current understanding of the pathophysiological mechanisms underlying thin endometrium and highlights emerging therapeutic approaches. Published studies indicate that impaired uterine perfusion and downregulation of vascular endothelial growth factor (VEGF) compromise angiogenesis, resulting in tissue-level reproductive defects. Hypoxia, together with the activation of the hypoxia-inducible factor 1-alpha (HIF-1α) and RhoA/Rho-associated protein kinase (ROCK) pathways, has been shown to disrupt epithelial cell integrity and exacerbate endometrial atrophy. Immune impairments characterized by abnormal cytokine signaling, reduced natural killer (NK) cell activity, and chronic endometritis further reduce endometrial tolerance. Additionally, epigenetic modifications, such as aberrant DNA methylation and microRNA (miRNA) dysregulation, have been linked to altered expression of key implantation-related genes, including homeobox A10 (HOXA10). Conventional therapies, such as estrogen supplementation, vasodilators, and granulocyte colony-stimulating factor (G-CSF), have variable efficacy. In contrast, regenerative strategies, including stem cell-based therapies, platelet-rich plasma (PRP), and biomaterial-based interventions, have shown promising potential for restoring endometrial function. A comprehensive understanding of these mechanisms is essential for improving diagnostic and therapeutic strategies, and while regenerative approaches represent a promising avenue for enhancing endometrial receptivity and reproductive success, further preclinical and clinical studies are warranted to optimize these novel therapies and evaluate their long-term safety and efficacy.

PMID:
40447929
Bibliographic data and abstract were imported from PubMed on 31 May 2025.

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