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Updated: Oct 16, 2025
Author Spotlight: Investigating the Mechanisms and Inducing Models of Polycystic Ovary Syndrome
Published on: July 5, 2024
Metformin improves epigenetic modification involved in oocyte growth and embryo development in polycystic ovary
Showra Amani Abkenari1, Leili Safdarian2, Fardin Amidi1,2
1Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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 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.
Insights
Metformin improves oocyte quality in polycystic ovary syndrome (PCOS) by reducing oxidative stress and epigenetic changes. This study investigated these effects in a mouse model, showing metformin
Area of Science:
- Reproductive Biology and Endocrinology
- Epigenetics and Developmental Origins of Health and Disease
Background:
- Polycystic ovary syndrome (PCOS) is linked to impaired oocyte quality, potentially due to epigenetic changes (ECs).
- The specific relationship between dehydroepiandrosterone (DHEA)-induced PCOS, ECs, and oocyte quality remains under-investigated.
Purpose of the Study:
- To investigate the relationship between impaired oocyte quality and ECs in a DHEA-induced PCOS mouse model.
- To evaluate the therapeutic effect of metformin on ECs and oocyte quality in this PCOS model.
Main Methods:
- Establishment of a DHEA-induced PCOS mouse model, divided into control, sham, DHEA, and DHEA + Metformin groups.
- Assessment of histone acetylation (H4K5, H4K16) and DNA methylation (5MeC, H3K9) via immunocytochemistry.
- Analysis of epigenetic gene expression (Hdac1, Hdac2, Dnmt1, Dnmt3a) using RT-PCR.
- Evaluation of mitochondrial membrane potential (MMP), oxidative stress (OS), embryo development, ovarian morphology, hormones, and AMPKα phosphorylation.
Main Results:
- Metformin treatment normalized estrous cycles, improved ovarian morphology, reduced sexual hormones and OS, and increased MMP and AMPKα phosphorylation in DHEA-treated mice.
- Metformin upregulated Dnmt1, Dnmt3a, and Hdac2 gene expression but did not affect Hdac1.
- Significant decreases in acetylated H4K16 and increases in methylated H3K9 were observed in MII oocytes of the metformin group compared to the DHEA group.
Conclusions:
- Metformin ameliorates DHEA-induced PCOS-related oocyte quality impairment in mice.
- Metformin enhances oocyte developmental competence by reducing oxidative stress and specific epigenetic alterations.
- The findings suggest metformin's potential as a therapeutic agent for improving oocyte quality in PCOS.
