Genome-wide methylation profiling in granulosa lutein cells of women with polycystic ovary syndrome (PCOS)
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Genome-wide methylation profiling in granulosa lutein cells of women with polycystic ovary syndrome (PCOS). / Makrinou, E.; Drong, A. W.; Christopoulos, G.; Lerner, A.; Chapa-Chorda, I.; Karaderi, T.; Lavery, S.; Hardy, K.; Lindgren, C. M.; Franks, S.
In: Molecular and Cellular Endocrinology, Vol. 500, 110611, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Genome-wide methylation profiling in granulosa lutein cells of women with polycystic ovary syndrome (PCOS)
AU - Makrinou, E.
AU - Drong, A. W.
AU - Christopoulos, G.
AU - Lerner, A.
AU - Chapa-Chorda, I.
AU - Karaderi, T.
AU - Lavery, S.
AU - Hardy, K.
AU - Lindgren, C. M.
AU - Franks, S.
N1 - Funding Information: E.M is funded by the Genesis Research Trust , as part of her Daphne Jackson Fellowship. C.M.L is supported by the Li Ka Shing Foundation , WT-SSI/John Fell funds and by the NIHR Biomedical Research Centre, Oxford , by Widenlife and NIH ( CRR00070 CR00.01 ). The work was also supported by grants to S.F and K.H from MRC ( G0802782 and MR/M012638/1 ). Funding Information: We would like to thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics (funded by Wellcome Trust grant reference 090532/Z/09/Z ) for the generation of Methylation data. Appendix A Publisher Copyright: © 2019
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - DNA methylation
KW - EWAS
KW - Metabolic syndrome
KW - PCOS
KW - Reproduction
U2 - 10.1016/j.mce.2019.110611
DO - 10.1016/j.mce.2019.110611
M3 - Journal article
C2 - 31600550
AN - SCOPUS:85074166900
VL - 500
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
SN - 0303-7207
M1 - 110611
ER -
ID: 301621794