The effect of mitochondria-targeted antioxidant MitoQ10 on redox signaling pathway components in PCOS mouse model.

PURPOSE: Considerable evidence suggests that mitochondrial dysfunction and oxidative stress contribute to the pathogenesis of Polycystic ovary syndrome (PCOS). We aimed to evaluate the effectiveness of mitochondria-targeted antioxidant, MitoQ10, on the redox signaling pathway's component in PCOS. METHOD: We assessed TXNIP, TRX, and ASK1 expression in granulosa cells (GCs) of the DHEA-induced PCOS mouse model. Female BALB/c mice in five groups of Control, DHEA, and DHEA + MitoQ10 in three doses of 250, 500, and 750 µmol/L MitoQ10 were treated for 21 days. RESULTS: Histological investigation showed a probable improvement in folliculogenesis; besides, ASK1 and TXNIP expression were significantly increased in GCs of the PCOS mouse F4Fmodel as compared to the control groups and decreased steadily in groups treated by MitoQ10. However, TRX expression showed a drop that was restored by MitoQ10 meaningfully (P ≤ 0.05). CONCLUSION: The work presented herein suggests mitochondria-targeted antioxidant, MitoQ10, have modulating effects on folliculogenesis in the ovary and also on the redox signaling pathway in GCs of PCOS mouse model which may have potential to attenuate oxidative stress and its relative damages.

Metformin improves epigenetic modification involved in oocyte growth and embryo development in polycystic ovary syndrome mice model.

The possible relationship between dehydroepiandrosterone (DHEA)-induced polycystic ovary syndrome (PCOS) and epigenetic changes (ECs) leading to the impaired oocyte quality, has not been investigated yet. So, this study aimed to provide an insight into the relationship of the impaired oocyte quality with ECs in a mice DHEA-induced PCOS model and to further reveal the effect of metformin treatment. For this purpose, 80 female BALB/C mice were randomly divided into four equal groups, named as the control, sham, (DHEA) and DHEA + Metformin groups. The alterations in acetylation of H4K5 and H4K16, and in methylation of DNA (5MeC) and H3K9 were evaluated using immunocytochemical. Moreover, the expression of Hdac1, Hdac2, Dnmt1, and Dnmt3a genes involved in ECs were analyzed using reverse-transcription polymerase chain reaction. As well, the levels of mitochondrial membrane potential (MMP), oxidative stress (OS), embryo development, ovarian morphology, sexual hormone, ovulatory function, and AMPKα phosphorylation activity were compared in all the studied groups. Metformin attenuated the damages induced by DHEA as indicated by the normalized the estrous cycle, the improved ovarian morphology, the decreased sexual hormone and OS levels, and the increased MMP and AMPKα phosphorylation levels. In the metformin group, the Dnmt1, Dnmt3a, and Hdac2 genes have significantly upregulated compared to the DHEA group. However, metformin was found to have no effect on the expression level of Hdac1. In this regard, significant decrease and increase were observed in both the acetylated H4K16 and methylated H3K9 within MII oocytes in the DHEA + Metformin group compared with the DHEA group. Our results show that metformin could enhance the developmental competence of PCOS oocytes via reducing OS and ECs.