# EZH2 promotes endometriosis progression through estrogen receptor and TNFα expression

## TL;DR

This study shows that EZH2 promotes endometriosis by reducing ERα and increasing TNFα, and that inhibiting EZH2 may help treat the condition.

## Contribution

The study reveals a novel mechanism involving EZH2, ERα/ERβ imbalance, and TNFα in endometriosis progression.

## Key findings

- EZH2 reduces ERα and increases ERβ binding to the TNFα promoter, raising inflammation.
- EZH2 inhibition with GSK343 reduced TNFα and endometriosis in mice.
- Human endometriotic tissue had higher EZH2 and ERβ and lower ERα than controls.

## Abstract

Endometriosis is a chronic inflammatory gynecological condition marked by the presence of tissue similar to the endometrium grows outside the uterus, often leading pelvic pain and infertility. This study explores how enhancer of zeste homolog 2 (EZH2) influences endometriosis, particularly through its interaction with estrogen receptors (ERs). We found that EZH2 reduces ERα expression, allowing ERβ to bind to the tumor necrosis factor α (TNFα) promoter and increase TNFα levels, fueling inflammation. In mice, the EZH2 inhibitor GSK343 reduced TNFα levels and endometriosis progression, similar to gene knockdown of ERβ or EZH2. In human samples, endometriotic tissue showed higher levels of EZH2 and ERβ and lower levels of ERα than in controls. Thus, EZH2 promotes TNFα-driven inflammation, contributing to endometriosis. Targeting EZH2, as with GSK343, could be a promising therapeutic strategy for endometriosis treatment.