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

多囊卵巢综合征 (PCOS) 女性的免疫细胞表观遗传重编程影响控制生殖功能的基因

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作者:Danielle Hiam, David Simar, Rhianna Laker, Ali Altıntaş, Melanie Gibson-Helm, Elly Fletcher, Alba Moreno-Asso, Adam J Trewin, Romain Barres, Nigel K Stepto

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.

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

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.

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