Mitochondria-targeted antioxidant therapy for an animal model of PCOS-IR

Polycystic ovary syndrome (PCOS) is a common endocrine disorder with unknown etiology and unsatisfactory clinical treatment. Considering the ethical limitations of studies involving humans, animal models that reflect features of PCOS and insulin resistance (IR) are crucial resources in investigating this syndrome. Our previous study showed that mitochondrial dysfunction resulted from pathogenic mutations of mitochondrial DNA (mtDNA), and that oxidative stress had an active role in the phenotypic manifestation of PCOS‑IR. Therefore, it was hypothesized that limiting oxidative stress and mitochondrial damage may be useful and effective for the clinical treatment of PCOS‑IR. For this purpose, the present study examined the therapeutic effects of the mitochondria‑targeted antioxidant MitoQ10 for PCOS‑IR. Furthermore, the histopathology was used to analysis the ovarian morphological changes. The endocrine and reproductive related parameters were analyzed by ELISA approach. A PCOS‑IR model was successfully established by subcutaneous injection of rats with testosterone propionate and feeding a high‑fat diet. The 30 female Sprague‑Dawley rats were then divided into three groups, comprising a control (n=10), animal model (PCOS‑IR, n=10) and MitoQ10 treatment (n=10) group. It was found that MitoQ10 significantly improved the IR condition and reversed the endocrine and reproductive conditions of PCOS. In addition, the impaired mitochondrial functions were improved following MitoQ10 administration. Notably, western blot results suggested that this antioxidant reduced the expression levels of apoptosis‑related proteins cytochrome c and B‑cell lymphoma‑2 (Bcl‑2)‑associated X protein, whereas the anti‑apoptotic protein Bcl‑extra large was increased following MitoQ10 treatment. Taken together, the data indicated that the MitoQ10 may have a beneficial favorable therapeutic effect on animals with PCOS‑IR, most likely via the protection of mitochondrial functions and regulation of programmed cell death‑related proteins.