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

Abstract

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.

Assessing the effect of MitoQ10 and Vitamin D3 on ovarian oxidative stress, steroidogenesis and histomorphology in DHEA induced PCOS mouse model

“…In the VDV group, 98% ethanol mixed distilled water at a dose of 100μl was injected daily via IP for 20 days. The MQ group mice were given 250μM (Sigma Aldrich, USA) of MitoQ 10 as the only source of drinking water for 20 days as previously stated [ 16 ]. Mice in V+M group received daily IP injection of Vitamin D3 (1 mg/kg body weight) dissolved in 98% ethanol and distilled water at a dose of 100 μl for 20 days while concurrently given 250μM of MitoQ 10 as the only source of drinking water.…”

Growth Hormone Activates PI3K/Akt Signaling and Inhibits ROS Accumulation and Apoptosis in Granulosa Cells of Patients With Polycystic Ovary Syndrome

“…Homodimers of Bcl-2 associate with the mitochondrial membrane and stabilize MMP. Upon apoptotic stimulation, Bax/Bcl-2 heterodimer decrease MMP, increase membrane's permeability and release cytochrome c, then activate caspase family [25,30]. Caspase-9 is cleaved and initiates caspase cascade to induce apoptosis [31].…”

Interplay between Oxidative Stress and Chronic Inflammation in PCOS: The Role of Genetic Variability in PCOS Risk and Treatment Responses

“…Not only did the antioxidant supplementation significantly improve oxidative status in those patients, but it also significantly affected pregnancy rate [52]. A recent study has also shown promising results with the mitochondria-targeted antioxidant for PCOS IR in animal model [53].…”