Epigenetic and Transcriptional Alterations in Human Adipose Tissue of Polycystic Ovary Syndrome

Abstract Genetic and epigenetic factors may predispose women to polycystic ovary syndrome (PCOS), a common heritable disorder of unclear etiology. Here we investigated differences in genome-wide gene expression and DNA methylation in adipose tissue from 64 women with PCOS and 30 controls. In total, 1720 unique genes were differentially expressed (Q < 0.05). Six out of twenty selected genes with largest expression difference (CYP1B1, GPT), genes linked to PCOS (RAB5B) or type 2 diabetes (PPARG, SVEP1), and methylation (DMAP1) were replicated in a separate case-control study. In total, 63,213 sites (P < 0.05) and 440 sites (Q < 0.15) were differently methylated. Thirty differentially expressed genes had corresponding changes in 33 different DNA methylation sites. Moreover, a total number of 1913 pairs of differentially expressed “gene-CpG” probes were significantly correlated after correction for multiple testing and corresponded with 349 unique genes. In conclusion, we identified a large number of genes and pathways that are affected in adipose tissue from women with PCOS. We also identified specific DNA methylation pathways that may affect mRNA expression. Together, these novel findings show that women with PCOS have multiple transcriptional and epigenetic changes in adipose tissue that are relevant for development of the disease.

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Transcriptional and Epigenetic Changes Influencing Skeletal Muscle Metabolism in Women With Polycystic Ovary Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2018-00935 ◽

2018 ◽

Vol 103 (12) ◽

pp. 4465-4477 ◽

Cited By ~ 18

Author(s):

Emma Nilsson ◽

Anna Benrick ◽

Milana Kokosar ◽

Anna Krook ◽

Eva Lindgren ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Dna Methylation ◽

Polycystic Ovary Syndrome ◽

Mrna Expression ◽

Polycystic Ovary ◽

Differentially Expressed ◽

Ovary Syndrome ◽

Cpg Sites

Abstract Context Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). Despite this, the mechanisms underlying insulin resistance in PCOS are largely unknown. Objective To investigate the genome-wide DNA methylation and gene expression patterns in skeletal muscle from women with PCOS and controls and relate them to phenotypic variations. Design/Participants In a case-control study, skeletal muscle biopsies from women with PCOS (n = 17) and age-, weight-, and body mass index‒matched controls (n = 14) were analyzed by array-based DNA methylation and mRNA expression profiling. Results Eighty-five unique transcripts were differentially expressed in muscle from women with PCOS vs controls, including DYRK1A, SYNPO2, SCP2, and NAMPT. Furthermore, women with PCOS had reduced expression of genes involved in immune system pathways. Two CpG sites showed differential DNA methylation after correction for multiple testing. However, an mRNA expression of ∼30% of the differentially expressed genes correlated with DNA methylation levels of CpG sites in or near the gene. Functional follow-up studies demonstrated that KLF10 is under transcriptional control of insulin, where insulin promotes glycogen accumulation in myotubes of human muscle cells. Testosterone downregulates the expression levels of COL1A1 and MAP2K6. Conclusion PCOS is associated with aberrant skeletal muscle gene expression with dysregulated pathways. Furthermore, we identified specific changes in muscle DNA methylation that may affect gene expression. This study showed that women with PCOS have epigenetic and transcriptional changes in skeletal muscle that, in part, can explain the metabolic abnormalities seen in these women.

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Erratum: Epigenetic and Transcriptional Alterations in Human Adipose Tissue of Polycystic Ovary Syndrome

Scientific Reports ◽

10.1038/srep25321 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 1

Author(s):

Milana Kokosar ◽

Anna Benrick ◽

Alexander Perfilyev ◽

Romina Fornes ◽

Emma Nilsson ◽

...

Keyword(s):

Adipose Tissue ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Human Adipose Tissue ◽

Ovary Syndrome ◽

Transcriptional Alterations

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Brown adipose tissue thermogenesis in women with polycystic ovary syndrome

Endocrine Abstracts ◽

10.1530/endoabs.49.gp135 ◽

2017 ◽

Cited By ~ 1

Author(s):

Soulmaz Shorakae ◽

Eveline Jona ◽

Courten Barbora de ◽

Gavin Lambert ◽

Elisabeth Lambert ◽

...

Keyword(s):

Adipose Tissue ◽

Polycystic Ovary Syndrome ◽

Brown Adipose Tissue ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis

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Identification of differentially expressed Long non-coding RNAs in follicular granulosa cells from polycystic ovary syndrome patients and controls

10.26226/morressier.573c1514d462b80296c98c63 ◽

2016 ◽

Author(s):

Zheng Yan

Keyword(s):

Polycystic Ovary Syndrome ◽

Granulosa Cells ◽

Polycystic Ovary ◽

Differentially Expressed ◽

Ovary Syndrome ◽

Non Coding Rnas

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Indirect Predictors of Visceral Adipose Tissue in Women with Polycystic Ovary Syndrome: A Comparison of Methods

Nutrients ◽

10.3390/nu13082494 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2494

Author(s):

Małgorzata Kałużna ◽

Magdalena Czlapka-Matyasik ◽

Aleksandra Bykowska-Derda ◽

Jerzy Moczko ◽

Marek Ruchala ◽

...

Keyword(s):

Adipose Tissue ◽

Polycystic Ovary Syndrome ◽

Visceral Adipose Tissue ◽

Polycystic Ovary ◽

Age Groups ◽

Ovary Syndrome ◽

Women Subjects ◽

Pcos Group ◽

Total Body ◽

Visceral Adipose

Visceral adipose tissue (VAT) accumulation, is a part of a polycystic ovary syndrome (PCOS) phenotype. Dual-energy x-ray absorptiometry (DXA) provides a gold standard measurement of VAT. This study aimed to compare ten different indirect methods of VAT estimation in PCOS women. The study included 154 PCOS and 68 age- and BMI-matched control women. Subjects were divided into age groups: 18–30 y.o. and 30–40 y.o. Analysis included: body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), waist/height 0.5 (WHT.5R), visceral adipose index (VAI), lipid accumulation product (LAP), and fat mass index (FMI). VAT accumulation, android-to-gynoid ratio (A/G), and total body fat (TBF) was measured by DXA. ROC analysis revealed that WHtR, WHT.5R, WC, BMI, and LAP demonstrated the highest predictive value in identifying VAT in the PCOS group. Lower cut-off values of BMI (23.43 kg/m2) and WHtR (0.45) were determined in the younger PCOS group and higher thresholds of WHtR (0.52) in the older PCOS group than commonly used. Measuring either: WHtR, WHT.5R, WC, BMI, or LAP, could help identify a subgroup of PCOS patients at high cardiometabolic risk. The current observations reinforce the importance of using special cut-offs to identify VAT, dependent on age and PCOS presence.

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