Epigenetic reprogramming of immune cells in women with PCOS impact genes controlling reproductive function
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Epigenetic reprogramming of immune cells in women with PCOS impact genes controlling reproductive function. / Hiam, Danielle; Simar, David; Laker, Rhianna; Altıntaş, Ali; Gibson-Helm, Melanie; Fletcher, Elly; Moreno-Asso, Alba; Trewin, Adam J; Barres, Romain; Stepto, Nigel K.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 104, No. 12, 2019, p. 6155-6170.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Epigenetic reprogramming of immune cells in women with PCOS impact genes controlling reproductive function
AU - Hiam, Danielle
AU - Simar, David
AU - Laker, Rhianna
AU - Altıntaş, Ali
AU - Gibson-Helm, Melanie
AU - Fletcher, Elly
AU - Moreno-Asso, Alba
AU - Trewin, Adam J
AU - Barres, Romain
AU - Stepto, Nigel K
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
U2 - 10.1210/jc.2019-01015
DO - 10.1210/jc.2019-01015
M3 - Journal article
C2 - 31390009
VL - 104
SP - 6155
EP - 6170
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 12
ER -
ID: 225522082