eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
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SCImago Journal & Country Rank
4/2019
vol. 15
 
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abstract:
Clinical research

Role of epigenetic modifications in the aberrant CYP19A1 gene expression in polycystic ovary syndrome

Elham Hosseini
,
Maryam Shahhoseini
,
Parvaneh Afsharian
,
Leila Karimian
,
Mahnaz Ashrafi
,
Fereshteh Mehraein
,
Reza Afatoonian

Arch Med Sci 2019; 15 (4): 887–895
Online publish date: 2019/06/19
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Introduction
In this study, the global DNA methylation, histone acetylation and methylation levels of cumulus cells (CCs) in infertile polycystic ovary syndrome (PCOS) patients and the correlation of these epigenetic modifications with the expression of the ovarian aromatase gene (as an important marker in the etiology of PCOS) were investigated.

Material and methods
A cross-sectional study was conducted on 24 patients (12 PCOS patients and 12 healthy women), who underwent ovarian stimulation. Nucleosome ELISA was performed, in order to identify the global occupancy level of Mecp2 (as a marker of DNA methylation) and H3K9me2/H3K9ac as histone modification markers in chromatin fractions obtained from CCs. The CYP19A1 gene expression was measured by qRT-PCR. The level of DNA incorporation of MeCP2, histone modification markers and binding of estrogen receptor  (ER) to CYP19A1 regulatory sequences were examined by ChIP-QPCR assay.

Results
The data demonstrate a significant increase in global occupancy levels of MeCP2 and H3K9ac markers and a decrease of H3K9me2 to chromatin in CCs of PCOS patients vs. control group. Furthermore, CYP19A1 gene expression, and the incorporation of H3K9ac in PII, PI.3, and PI.4 promoters of CYP19A1 in PCOS, were higher than those of controls. Also, significant hypomethylation of H3K9 at PII and DNA hypomethylated at PII and PI.3 promoters and differential binding of ER to three promoters were observed in PCOS patients (p < 0.05).

Conclusions
Aromatase expression can be affected by epigenetic modifications and differential ER binding to the proximal CYP19A1 promoters. These mechanisms may be involved in the enhanced aromatase transcription during ovarian stimulation in PCOS patients.

keywords:

polycystic ovary syndrome, epigenetic, CYP19A1, cumulus cell, estrogen receptor β

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