SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

Early onset pre-eclampsia is associated with altered DNA methylation of cortisol-signalling and steroidogenic genes in the placenta.

Hogg, K; Blair, JD; McFadden, DE; von Dadelszen, P; Robinson, WP (2013) Early onset pre-eclampsia is associated with altered DNA methylation of cortisol-signalling and steroidogenic genes in the placenta. PLoS One, 8 (5). ISSN 1932-6203 https://doi.org/10.1371/journal.pone.0062969
SGUL Authors: von Dadelszen, Peter

[img]
Preview
PDF Published Version
Available under License Creative Commons Attribution.

Download (852kB) | Preview

Abstract

Placental cortisol is inactivated in normotensive pregnancies, but is frequently present in pre-eclampsia associated placentae. Since glucocorticoids are strongly associated with the programming of long-term health, we assessed DNA methylation of genes involved in cortisol signalling and bioavailability, and hormonal signalling in the placenta of normotensive and hypertensive pregnancies. Candidate genes/CpG sites were selected through analysis of Illumina Infinium HumanMethylation450 BeadChip array data on control (n = 19) and early onset pre-eclampsia (EOPET; n = 19) placental samples. DNA methylation was further quantified by bisulfite pyrosequencing in a larger cohort of control (n = 111) cases, in addition to EOPET (n = 19), late onset pre-eclampsia (LOPET; n = 18) and normotensive intrauterine growth restriction (nIUGR; n = 13) cases. DNA methylation (percentage points) was increased at CpG sites within genes encoding the glucocorticoid receptor (NR3C1 exon 1D promoter; +8.46%; P<0.01) and corticotropin releasing hormone (CRH) binding protein (CRHBP intron 3; +9.14%; P<0.05), and decreased within CRH (5' UTR; -4.30%; P = 0.11) in EOPET-associated placentae, but not in LOPET nor nIUGR cases, compared to controls. Differential DNA methylation was not observed among groups at the 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) gene promoter. Significant hypomethylation was observed in pre-eclampsia but not nIUGR placentae for steroidogenic genes, including CYP11A1 (exon1; EOPET; -9.66%; P<0.00001, and LOPET; -5.77%; P<0.001), 3β-hydroxy-delta-5-steroid dehydrogenase type 1 (HSD3B1 exon 2; EOPET; -12.49%; P<0.00001, and LOPET; -6.88%; P<0.001), TEA domain family member 3 (TEAD3 intron 1; EOPET; -12.56%; P<0.00001) and CYP19 (placental-specific exon 1.1 promoter; EOPET; -10.62%, P<0.0001). These data represent dysregulation of the placental epigenome in pre-eclampsia related to genes involved in maintaining the hormonal environment during pregnancy and highlights particular susceptibility in the early onset syndrome.

Item Type: Article
Additional Information: Copyright: © 2013 Hogg et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Adult, DNA Methylation, Exons, Female, Gestational Age, Glucocorticoids, Humans, Hydrocortisone, Labor Onset, Male, Placenta, Pre-Eclampsia, Pregnancy, RNA, Messenger, Receptors, Glucocorticoid, Signal Transduction, Stress, Physiological, Time Factors, Placenta, Humans, Pre-Eclampsia, Hydrocortisone, Receptors, Glucocorticoid, RNA, Messenger, Glucocorticoids, Signal Transduction, DNA Methylation, Gestational Age, Pregnancy, Labor Onset, Exons, Time Factors, Adult, Female, Male, Stress, Physiological, General Science & Technology, MD Multidisciplinary
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: PLoS One
Article Number: e62969
ISSN: 1932-6203
Language: eng
Dates:
DateEvent
7 May 2013Published
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
FRN-119402Canadian Institutes of Health ResearchUNSPECIFIED
PubMed ID: 23667551
Go to PubMed abstract
URI: http://sgultest.da.ulcc.ac.uk/id/eprint/107502
Publisher's version: https://doi.org/10.1371/journal.pone.0062969

Actions (login required)

Edit Item Edit Item