Mitofusin 2 Attenuates Adenomyosis Progression by Suppressing Epithelial-Mesenchymal Transition: Evidence From Clinical and Experimental Models

Background: Adenomyosis involves epithelial-mesenchymal transition (EMT), yet the role of mitochondrial regulator Mitofusin 2 (Mfn2) remains unclear. This study investigated the role of Mfn2 in adenomyosis-related EMT and evaluated its potential as a therapeutic target. Methods: Mfn2 expression was compared between human adenomyotic and normal endometrial tissues using immunohistochemistry. Transforming growth factor-beta 1 (TGF-β1)-induced EMT was established in Ishikawa cells, and Mfn2 was overexpressed to assess EMT markers using quantitative polymerase chain reaction (qPCR) and Western blot, as well as cell migration and invasion (via scratch and Transwell assays). A neonatal mouse model of tamoxifen-induced adenomyosis received intrauterine lentiviral Mfn2 overexpression. Uterine morphology, fibrosis, and EMT markers were evaluated after 20 days. Results: Mfn2 was significantly downregulated in adenomyosis (p < 0.05). Overexpression of Mfn2 reversed EMT, evidenced by increased E-cadherin and decreased N-cadherin and Vimentin (p < 0.05), suppressed cell migration and invasion in vitro (p < 0.05), improved uterine morphology (p < 0.05), reduced fibrosis (p < 0.05), and inhibited EMT in vivo. Conclusion: Mfn2 suppresses EMT in adenomyosis, suggesting its protective role and potential as a therapeutic target.