p53-mediated epigenetic regulation in the pathogenesis of endometriosis.

Endometriosis (EMs) is a common gynecological disorder affecting reproductive‑aged women, characterized by ectopic endometrial growth and chronic pelvic pain that severely impairs quality of life. Although its pathogenesis remains incompletely understood, accumulating evidence indicates that the tumor suppressor p53 and aberrant epigenetic modifications play critical roles in EMs initiation and progression. p53 expression is significantly reduced in ectopic lesions, leading to apoptosis resistance and hyperproliferation of endometrial cells. Importantly, p53 dysfunction contributes to EMs through at least four epigenetic mechanisms: (1) p53 transcriptionally represses DNA methyltransferases (DNMTs), and its loss indirectly promotes locus‑specific hypermethylation and silencing of tumor suppressors; (2) p53, via its interaction with histone modifiers, influences their recruitment to target genes, and p53 impairment synergizes with histone deacetylase dysregulation to create a pro‑proliferative, anti‑apoptotic microenvironment; (3) p53 functionally interacts with the chromatin remodeler ARID1A, and their co‑dysruption impairs chromatin accessibility and immune homeostasis; (4) p53 coordinates non‑coding RNA networks (e.g. lncRNA MALAT1, miR‑34a) that regulate epithelial-mesenchymal transition, angiogenesis, and apoptosis. This review systematically summarizes the p53‑mediated epigenetic regulatory network in EMs and highlights potential therapeutic opportunities targeting p53-epigenetic crosstalk. Future studies should investigate synergistic mechanisms among different epigenetic layers and validate these findings in multi‑center clinical cohorts.