Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology

Just Accepted

This article has been peer reviewed and accepted for publication. It is in production and has not been edited, so may differ from the final published form.

Intracytoplasmic Oxidative Stress Reverses Epigenetic Modifications in Polycystic Ovary Syndrome

Fatemeh Eini , Marefat Ghaffari Novin , Khojasteh Joharchi , Ahmad Hosseini , Hamid Nazarian , Abbas Piryaei , Arash Bidadkosh

Abstract

In polycystic ovary syndrome, substantial genetic and environmental alterations along with hyperandrogenism affect quality of oocytes and decreases ovulation rates. To determine the mechanisms of these alterations, specifically due to the rise of plasma androgens, the present study was designed in experimentally-induced PCOS mice. The adult female B6D2F1 mice were treated with dehydroepiandrosterone. After twenty days, oocytes at germinal vesicle and metaphase II stages were retrieved in isolated ovaries, and subsequent analyses of oocyte quality were performed for each mouse. Dehydroepiandrosterone treatment resulted in excessive abnormal morphology and decreased polar body extrusion rate in oocytes, and was associated with increase in oxidative stress. Analysis of fluorescence intensity revealed a significant reduction of DNA methylation and dimethylation of histone H3 at lysine-9 in dehydroepiandrosterone-treated oocytes, which was associated with increased acetylation of histone H4 at lysine-12. Similarly, expression of DNA methyltransferase-1 and histone deacetylase-1 enzymes was significantly decreased in dehydroepiandrosterone-treated mice. There was a significant correlation between excessive reactive oxygen species production and increased histone acetylation, which is a novelty and can provide new insights for the mechanism of polycystic ovary syndrome. Our results indicated that epigenetic modifications of oocyte possibly affect the quality of maturation and the ovulation rates in polycystic ovary syndrome, and the probable mechanism might be the augmentation of intracytoplasmic reactive oxygen species.

RD16428  Accepted 09 March 2017

© CSIRO 2017