Epigenetic reprogramming of immune cells in women with PCOS impact genes controlling reproductive function

Research output: Contribution to journalJournal articlepeer-review

  • Danielle Hiam
  • David Simar
  • Rhianna Laker
  • Altintas, Ali
  • Melanie Gibson-Helm
  • Elly Fletcher
  • Alba Moreno-Asso
  • Adam J Trewin
  • Barrès, Romain
  • Nigel K Stepto

CONTEXT: Polycystic ovary syndrome (PCOS) is a chronic disease affecting reproductive function and whole-body metabolism. While the aetiology 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 to controls and if 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 MEASURE(S): Isolated peripheral blood mononuclear cells were analysed using multi-colour flow cytometry methods to determine global DNA methylation levels in a cell specific fashion. Transcriptomic and genome-wide DNA methylation analysis was 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), 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 5,581 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 remodelling 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.

Original languageEnglish
JournalJournal of Clinical Endocrinology and Metabolism
Issue number12
Pages (from-to)6155-6170
Publication statusPublished - 2019

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