Metformin improves epigenetic modification involved in oocyte growth and embryo development in polycystic ovary syndrome mice model
Autor: | Ali Hosseini, Leili Safdarian, Aligholi Sobhani, Elnaz Salahi, Roya Aryanpour, Showra Amani Abkenari, Fardin Amidi |
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Rok vydání: | 2021 |
Předmět: |
medicine.medical_specialty
endocrine system diseases Embryonic Development Dehydroepiandrosterone Biology medicine.disease_cause Epigenesis Genetic Mice Internal medicine Genetics medicine Animals Epigenetics Estrous cycle Mice Inbred BALB C Cell Biology Oocyte Polycystic ovary Metformin Endocrinology medicine.anatomical_structure Oocytes Female hormones hormone substitutes and hormone antagonists Oxidative stress Polycystic Ovary Syndrome Developmental Biology Hormone medicine.drug |
Zdroj: | Molecular Reproduction and Development. 88:817-829 |
ISSN: | 1098-2795 1040-452X |
Popis: | 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. |
Databáze: | OpenAIRE |
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