Metformin improves epigenetic modification involved in oocyte growth and embryo development in polycystic ovary syndrome mice model. Issue 12 (17th October 2021)

• Record Type: Journal Article
• Authors: Amani Abkenari, Showra; Safdarian, Leili; Amidi, Fardin; Hosseini, Ali; Aryanpour, Roya; Salahi, Elnaz; Sobhani, Aligholi
• Is Part Of: Molecular reproduction and development. Volume 88:Issue 12(2021)
• Page Start: 817
• Page End: 829
• Publication Date: 2021-10-17
• Subjects: acetylation -- dehydroepiandrosterone -- metformin -- methylation; Reproduction -- Periodicals; Molecular biology -- Periodicals; Molecular genetics -- Periodicals; Embryology -- Periodicals; 571.8
• DOI: 10.1002/mrd.23537
• Languages: English
• ISSNs: 1040-452X

Abstract

Abstract: 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 Hdac 2 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.