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Epigenetic Reprogramming of Immune Cells in Women with PCOS Impact Genes Controlling Reproductive Function

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Version 2 2024-06-04, 12:59
Version 1 2019-09-19, 08:13
journal contribution
posted on 2024-06-04, 12:59 authored by Danielle HiamDanielle Hiam, D Simar, R Laker, A Altlntaş, M Gibson-Helm, E Fletcher, A Moreno-Asso, AJ Trewin, R Barres, NK Stepto
Abstract Context Polycystic ovary syndrome (PCOS) is a chronic disease affecting reproductive function and whole-body metabolism. Although the etiology is unclear, emerging evidence indicates that the epigenetics may be a contributing factor. Objective To determine the role of global and genome-wide epigenetic modifications in specific immune cells in PCOS compared with controls and whether these could be related to clinical features of PCOS. Design Cross-sectional study. Participants Women with (n = 17) or without PCOS (n = 17). Setting Recruited from the general community. Main Outcome Measures Isolated peripheral blood mononuclear cells were analyzed using multicolor flow cytometry methods to determine global DNA methylation levels in a cell-specific fashion. Transcriptomic and genome-wide DNA methylation analyses were performed on T helper cells using RNA sequencing and reduced representation bisulfite sequencing. Results Women with PCOS had lower global DNA methylation in monocytes (P = 0.006) and in T helper (P = 0.004), T cytotoxic (P = 0.004), and B cells (P = 0.03). Specific genome-wide DNA methylation analysis of T helper cells from women with PCOS identified 5581 differentially methylated CpG sites. Functional gene ontology enrichment analysis showed that genes located at the proximity of differentially methylated CpG sites belong to pathways related to reproductive function and immune cell function. However, these genes were not altered at the transcriptomic level. Conclusions It was shown that PCOS is associated with global and gene-specific DNA methylation remodeling in a cell type–specific manner. Further investigation is warranted to determine whether epigenetic reprogramming of immune cells is important in determining the different phenotypes of PCOS.

History

Journal

Journal of Clinical Endocrinology and Metabolism

Volume

104

Pagination

6155-6170

Location

United States

Open access

  • Yes

ISSN

0021-972X

eISSN

1945-7197

Language

English

Publication classification

C1.1 Refereed article in a scholarly journal

Issue

12

Publisher

ENDOCRINE SOC