Dimethyl Fumarate Ameliorates the Endometriosis Through Anti-Inflammatory and Anti-Proliferation Mechanisms In Vitro and In Vivo

Abstract

Dimethyl fumarate is a widely known therapeutic agent with anti-inflammatory properties for psoriasis and multiple sclerosis. Despite the current attempts to use dimethyl fumarate for treating various inflammatory diseases, its effects on endometriosis have not been previously reported. Endometriosis is a genital disease that causes various health problems in women, and treatment methods targeting the inflammatory environment are being attempted. Therefore, it is hypothesized that dimethyl fumarate has therapeutic effects on endometriosis through its anti-inflammatory effects. Dimethyl fumarate exerted remarkable effects on cellular mechanisms, including reactive oxygen species production, activation of mitogen‑activated protein kinase signals, loss of mitochondrial function, and disruption of calcium ion homeostasis in the immortalized human ovarian endometrial stromal cells. In an endometriosis mouse model, dimethyl fumarate downregulated cell cycle-related genes and induced inhibitory effects on endometriosis lesion growth. In particular, the immune cell population and expression of inflammatory cytokines such as IL-1β, IL-6, and IL-10 are regulated by dimethyl fumarate. These results support its potential as a therapeutic agent to control the excessive inflammatory environment in patients with endometriosis. This study identifies for the first time that dimethyl fumarate, which is already in clinical use, can be used to treat endometriosis.