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Genome-wide methylation profiling in granulosa lutein cells of women with polycystic ovary syndrome (PCOS).

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Title: Genome-wide methylation profiling in granulosa lutein cells of women with polycystic ovary syndrome (PCOS).
Authors: Makrinou, E
Drong, AW
Christopoulos, G
Lerner, A
Chapa-Chorda, I
Karaderi, T
Lavery, S
Hardy, K
Lindgren, CM
Franks, S
Item Type: Journal Article
Abstract: Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age, whose aetiology remains unclear. To improve our understanding of the molecular mechanisms underlying the disease, we conducted a genome-wide DNA methylation profiling in granulosa lutein cells collected from 16 women suffering from PCOS, in comparison to 16 healthy controls. Samples were collected by follicular aspiration during routine egg collection for IVF treatment. Study groups were matched for age and BMI, did not suffer from other disease and were not taking confounding medication. Comparing women with polycystic versus normal ovarian morphology, after correcting for multiple comparisons, we identified 106 differentially methylated CpG sites with p-values <5.8 × 10-8 that were associated with 88 genes, several of which, are known to relate either to PCOS or to ovarian function. Replication and validation of the experiment was done using pyrosequencing to analyse six of the identified differentially methylated sites. Pathway analysis indicated potential disruption in canonical pathways and gene networks that are, amongst other, associated with cancer, cardiogenesis, Hedgehog signalling and immune response. In conclusion, these novel findings indicate that women with PCOS display epigenetic changes in ovarian granulosa cells that may be associated with the heterogeneity of the disorder.
Issue Date: 7-Oct-2019
Date of Acceptance: 4-Oct-2019
URI: http://hdl.handle.net/10044/1/74400
DOI: https://doi.org/10.1016/j.mce.2019.110611
ISSN: 0303-7207
Publisher: Elsevier
Start Page: 1
End Page: 11
Journal / Book Title: Molecular and Cellular Endocrinology
Volume: 500
Copyright Statement: © 2019 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor/Funder: MRC
Daphne Jackson Trust
Genesis Research Trust
Funder's Grant Number: G0802782
N/A
01046
Keywords: DNA methylation
EWAS
Metabolic syndrome
PCOS
Reproduction
DNA methylation
EWAS
Metabolic syndrome
PCOS
Reproduction
Endocrinology & Metabolism
06 Biological Sciences
11 Medical and Health Sciences
07 Agricultural and Veterinary Sciences
Publication Status: Published
Conference Place: Ireland
Online Publication Date: 2019-10-07
Appears in Collections:Department of Metabolism, Digestion and Reproduction