Danielle Hiam1, David Simar2, Rhianna Laker3, Ali Altıntaş3, Melanie Gibson-Helm4, Elly Fletcher5, Alba Moreno-Asso1, Adam J Trewin1, Romain Barres3, Nigel K Stepto1,4,6. 1. Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia. 2. Mechanisms of Disease and Translational Research, School of Medical Sciences, UNSW Sydney, Sydney, New South Wales, Australia. 3. Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. 4. Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. 5. Baker Heart and Disease Institute, Melbourne, Victoria, Australia. 6. Medicine-Western Health, School of Medicine, Faculty of Medicine, Dentistry, and Health Science, Melbourne, Australia.
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.
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.
Authors: Alba Moreno-Asso; Ali Altıntaş; Luke C McIlvenna; Rhiannon K Patten; Javier Botella; Andrew J McAinch; Raymond J Rodgers; Romain Barrès; Nigel K Stepto Journal: J Mol Endocrinol Date: 2021-12-03 Impact factor: 5.098
Authors: Luke C McIlvenna; Rhiannon K Patten; Andrew J McAinch; Raymond J Rodgers; Nigel K Stepto; Alba Moreno-Asso Journal: Front Endocrinol (Lausanne) Date: 2021-10-11 Impact factor: 5.555
Authors: Ada Cheung; Nir Eynon; Patrice R Jones; Sarah Voisin; Brendan J Nolan; Shanie Landen; Macsue Jacques; Beau Newell; Sav Zwickl; Teddy Cook; Alex Wong; Ariel Ginger; Andrew Palmer; Andrew Garnham; Javier Alvarez-Romero; Namitha Mohandas; Kirsten Seale Journal: BMJ Open Date: 2022-05-11 Impact factor: 3.006
Authors: Danielle Hiam; Alba Moreno-Asso; Helena J Teede; Joop S E Laven; Nigel K Stepto; Lisa J Moran; Melanie Gibson-Helm Journal: J Clin Med Date: 2019-10-03 Impact factor: 4.241