Mitochondria-targeted antioxidant mitoquinone attenuates TGF-β-induced fibrosis and restores impaired decidualization in mouse endometrial stromal cells.

This study aimed to investigate the therapeutic effects of mitoquinone (MitoQ) in endometrial fibrosis and to examine its role in restoring impaired decidualization associated with intrauterine adhesion. We further sought to delineate the underlying mechanisms through which MitoQ exerts its protective effects. Finally, we propose mitochondrial-targeted antioxidant therapy as a potential strategy for the treatment of gynecological diseases. An in vitro mouse endometrial fibrosis model was established by treating mouse endometrial stromal cells with transforming growth factor-β (TGF-β). MitoQ was subsequently administered to fibrotic cells to evaluate its therapeutic effects on fibrosis and defective decidualization. These effects were analyzed using quantitative real-time polymerase chain reaction, immunoblotting, immunofluorescence staining, and additional molecular and cellular assays. The underlying mechanisms were further investigated. TGF-β treatment (5 ng/mL for 48 hours) effectively induced a markedly fibrotic phenotype in mouse endometrial stromal cells. These cells were subsequently treated with 1 μM MitoQ for 24 hours. MitoQ treatment significantly reduced collagen type I alpha 1 chain (COL1A1) expression at both the mRNA and protein levels and downregulated inflammation-related markers. These effects were accompanied by reduced mitochondrial stress and suppression of suppressor of mothers against decapentaplegic (SMAD) signaling. Furthermore, MitoQ treatment restored impaired decidualization in fibrotic cells, as supported by increased expression of prolactin and insulin-like growth factor binding protein 1 (IGFBP1). MitoQ treatment effectively attenuates TGF-β-induced endometrial fibrosis by reducing collagen deposition and inflammatory marker expression, while restoring impaired decidualization. These findings suggest that MitoQ may serve as a promising therapeutic candidate for fibrosis-associated uterine dysfunction.