MGST3 Promotes Endometriosis Progression by Suppressing Ferroptosis

Endometriosis (EMs) is characterized by dysregulated persistence and enhanced invasiveness of ectopic endometrial cells. Current treatment strategies remain limited by high recurrence rates and considerable adverse effects. Although iron overload is a recognized feature of EMs, ectopic lesions paradoxically demonstrate resistance to ferroptosis, an iron-dependent cell death mechanism. The mechanistic involvement of microsomal glutathione S-transferase 3 (MGST3) in this process remains to be clarified. This study examined MGST3 expression and its functional role in EMs using in vitro assays and an in vivo murine model. MGST3 expression was markedly increased in ectopic endometrial cells compared with controls. Functional analyses indicated that MGST3 enhances the invasive phenotype of immortalized human ectopic endometrial stromal cells while concurrently inhibiting apoptosis. Furthermore, treatment with GSTO-IN-2 in the mouse model attenuated ectopic lesion growth and significantly altered ferroptosis-associated markers. However, due to the lack of specificity of GSTO-IN-2 for MGST3, these in vivo findings cannot be directly attributed to an MGST3-specific effect. Collectively, these results indicate that MGST3 may play a role in the regulation of ferroptosis in EMs, with its overexpression contributing to ferroptosis-associated survival phenotypes in endometrial stromal cells. MGST3 may therefore serve as a potential biomarker and requires further investigation as a therapeutic target in EMs.