Insights into the Molecular Mechanisms and Signaling Pathways of Epithelial to Mesenchymal Transition (EMT) in the Pathophysiology of Endometriosis

Abstract

Endometriosis is a disease characterized by the presence of endometrial glands and stroma outside of the uterine corpus, often clinically presenting with pain and/or infertility. Ectopic lesions exhibit features characteristic of epithelial-to-mesenchymal transition (EMT), a process in which epithelial cells lose polarity and acquire mesenchymal traits, including migratory and invasive capabilities. During the process of EMT, epithelial traits are downregulated, while mesenchymal traits are acquired, with cells developing migratory ability, increasing proliferation, and resistance to apoptosis. EMT is promoted by exposure to hypoxia and stimulation by transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF), and estradiol. Signaling pathways that promote EMT are activated in most ectopic lesions and involve transcription factors such as Snail, Slug, ZEB-1/2, and TWIST-1/2. EMT-specific molecules present in the serum of women with endometriosis appear to have diagnostic potential. Strategies targeting EMT in animal models of endometriosis have demonstrated regression of ectopic lesions, opening the door for novel therapeutic approaches. This review summarizes the current understanding of the role of EMT in endometriosis and highlights potential targets for EMT-related diagnosis and therapeutic interventions.

Keywords: TGF-β; endometriosis; epithelial-to-mesenchymal transition; fibrosis.

Figure 1

Epithelial-to-mesenchymal transition (EMT) and its role in endometriosis pathophysiology. EMT is triggered by various stimuli, including TGF-β, hypoxia, estrogen, PDGF, and genetic mutations. These triggers induce the expression of EMT transcription factors such as Snail, Slug, Twist, ZEB1/2, and FOXC2, leading to the transition of epithelial cells into mesenchymal-like cells. This transition is marked by decreased epithelial markers (e.g., E-cadherin, cytokeratin, claudin 3/4/7) and increased mesenchymal markers (e.g., N-cadherin, vimentin). As a result, cells gain enhanced migratory capacity, proliferative ability, invasiveness, resistance to apoptosis, and contribute to fibrosis in endometriosis lesion formation and progression.