Genome-wide methylation profiling in granulosa lutein cells of women with polycystic ovary syndrome (PCOS)

E Makrinou; A W Drong; G Christopoulos; A Lerner; I Chapa-Chorda; T Karaderi; S Lavery; K Hardy; C M Lindgren; S Franks

doi:10.1016/j.mce.2019.110611

Genome-wide methylation profiling in granulosa lutein cells of women with polycystic ovary syndrome (PCOS)

Mol Cell Endocrinol. 2020 Jan 15:500:110611. doi: 10.1016/j.mce.2019.110611. Epub 2019 Oct 7.

Authors

E Makrinou¹, A W Drong², G Christopoulos³, A Lerner⁴, I Chapa-Chorda⁴, T Karaderi⁵, S Lavery³, K Hardy⁴, C M Lindgren⁶, S Franks⁴

Affiliations

¹ Imperial College London, Faculty of Medicine, Institute of Reproductive and Developmental Biology, London, W12 0NN, UK. Electronic address: e.makrinou@ucl.ac.uk.
² Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, OX3 7LF, UK.
³ IVF Unit, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, W12 0NN, UK.
⁴ Imperial College London, Faculty of Medicine, Institute of Reproductive and Developmental Biology, London, W12 0NN, UK.
⁵ Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK; Department of Biological Sciences, Faculty of Arts and Sciences, Eastern Mediterranean University, Famagusta, Cyprus.
⁶ Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, OX3 7LF, UK; Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.

Abstract

Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age, whose aetiology remains unclear. To improve our understanding of the molecular mechanisms underlying the disease, we conducted a genome-wide DNA methylation profiling in granulosa lutein cells collected from 16 women suffering from PCOS, in comparison to 16 healthy controls. Samples were collected by follicular aspiration during routine egg collection for IVF treatment. Study groups were matched for age and BMI, did not suffer from other disease and were not taking confounding medication. Comparing women with polycystic versus normal ovarian morphology, after correcting for multiple comparisons, we identified 106 differentially methylated CpG sites with p-values <5.8 × 10^-8 that were associated with 88 genes, several of which are known to relate either to PCOS or to ovarian function. Replication and validation of the experiment was done using pyrosequencing to analyse six of the identified differentially methylated sites. Pathway analysis indicated potential disruption in canonical pathways and gene networks that are, amongst other, associated with cancer, cardiogenesis, Hedgehog signalling and immune response. In conclusion, these novel findings indicate that women with PCOS display epigenetic changes in ovarian granulosa cells that may be associated with the heterogeneity of the disorder.

Keywords: DNA methylation; EWAS; Metabolic syndrome; PCOS; Reproduction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Case-Control Studies
DNA Methylation*
DNA Mutational Analysis
Epigenesis, Genetic
Female
Gene Regulatory Networks
Humans
Luteal Cells / chemistry*
Polycystic Ovary Syndrome / genetics*
Whole Genome Sequencing / methods*

Abstract

Publication types

MeSH terms

Grants and funding