An unbalanced diet in pregnancy associates with offspring epigenetic changes in genes controlling glucocorticoid action and fetal growth
An unbalanced diet in pregnancy associates with offspring epigenetic changes in genes controlling glucocorticoid action and fetal growth
OBJECTIVE: In epidemiological studies, adverse early-life conditions associate with subsequent cardiometabolic disease. Hypothesized causes include maternal malnutrition, foetal glucocorticoid overexposure and reduced growth factors. Animal studies suggest a role for epigenetic processes in maintaining early-life effects into adulthood, but human relevance is unknown. We aimed to investigate relationships between an unbalanced maternal diet in pregnancy, neonatal and adult anthropometric variables with methylation at key genes controlling tissue glucocorticoid action and foetal growth.
DESIGN: We studied 34 individuals aged 40 from the Motherwell cohort study whose mothers ate an unbalanced diet in pregnancy, previously linked with elevated blood pressure and cortisol in adult offspring.
MEASUREMENTS: DNA methylation at 11?-hydroxysteroid dehydrogenase type 2 (HSD2), glucocorticoid receptor (GR) and insulin-like growth factor 2 (IGF2) was measured by pyrosequencing on buffy coat DNA.
RESULTS: Methylation at specific CpGs in the HSD2 promoter and at one of the IGF2 differentially methylated regions (H19 ICR) correlated with neonatal anthropometric variables. CpG methylation within HSD2, GR and H19 ICR was positively associated with increased adiposity and blood pressure in adulthood. Methylation at GR (exon 1F) was increased in offspring of mothers with the most unbalanced diets in pregnancy.
CONCLUSIONS: Alterations in DNA methylation at genes important in regulating circulating cortisol levels, tissue glucocorticoid action, blood pressure and foetal growth are present in adulthood in association with both early-life parameters and cardiometabolic risk factors. The data indicate a persisting epigenetic link between early-life maternal diet and/or foetal growth and cardiovascular disease risk in humans
808-815
Drake, A.J.
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McPherson, R.C.
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Godfrey, K.M.
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Cooper, C.
e05f5612-b493-4273-9b71-9e0ce32bdad6
Lillycrop, K.A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Hanson, M.A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Meehan, R.R.
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Seckl, J
285725dd-c265-4c2a-8870-87fc858d4362
Reynolds, R.M.
c58e0f89-329d-4e4e-be3f-3c53b2a847cc
December 2012
Drake, A.J.
2b0995aa-fdf9-47f7-a343-1eabd9bbb912
McPherson, R.C.
3994d9f8-3d82-4360-8421-9801cd78b409
Godfrey, K.M.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Cooper, C.
e05f5612-b493-4273-9b71-9e0ce32bdad6
Lillycrop, K.A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Hanson, M.A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Meehan, R.R.
6e8a2651-6492-48ab-9cdc-17024a6237ae
Seckl, J
285725dd-c265-4c2a-8870-87fc858d4362
Reynolds, R.M.
c58e0f89-329d-4e4e-be3f-3c53b2a847cc
Drake, A.J., McPherson, R.C., Godfrey, K.M., Cooper, C., Lillycrop, K.A., Hanson, M.A., Meehan, R.R., Seckl, J and Reynolds, R.M.
(2012)
An unbalanced diet in pregnancy associates with offspring epigenetic changes in genes controlling glucocorticoid action and fetal growth.
Clinical Endocrinology, 77 (6), .
(doi:10.1111/j.1365-2265.2012.04453.x).
(PMID:22642564)
Abstract
OBJECTIVE: In epidemiological studies, adverse early-life conditions associate with subsequent cardiometabolic disease. Hypothesized causes include maternal malnutrition, foetal glucocorticoid overexposure and reduced growth factors. Animal studies suggest a role for epigenetic processes in maintaining early-life effects into adulthood, but human relevance is unknown. We aimed to investigate relationships between an unbalanced maternal diet in pregnancy, neonatal and adult anthropometric variables with methylation at key genes controlling tissue glucocorticoid action and foetal growth.
DESIGN: We studied 34 individuals aged 40 from the Motherwell cohort study whose mothers ate an unbalanced diet in pregnancy, previously linked with elevated blood pressure and cortisol in adult offspring.
MEASUREMENTS: DNA methylation at 11?-hydroxysteroid dehydrogenase type 2 (HSD2), glucocorticoid receptor (GR) and insulin-like growth factor 2 (IGF2) was measured by pyrosequencing on buffy coat DNA.
RESULTS: Methylation at specific CpGs in the HSD2 promoter and at one of the IGF2 differentially methylated regions (H19 ICR) correlated with neonatal anthropometric variables. CpG methylation within HSD2, GR and H19 ICR was positively associated with increased adiposity and blood pressure in adulthood. Methylation at GR (exon 1F) was increased in offspring of mothers with the most unbalanced diets in pregnancy.
CONCLUSIONS: Alterations in DNA methylation at genes important in regulating circulating cortisol levels, tissue glucocorticoid action, blood pressure and foetal growth are present in adulthood in association with both early-life parameters and cardiometabolic risk factors. The data indicate a persisting epigenetic link between early-life maternal diet and/or foetal growth and cardiovascular disease risk in humans
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e-pub ahead of print date: 9 November 2012
Published date: December 2012
Organisations:
Human Development & Health
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Local EPrints ID: 367326
URI: http://eprints.soton.ac.uk/id/eprint/367326
PURE UUID: c013f08f-c0a4-4f49-8170-56dfdc0b765b
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Date deposited: 26 Aug 2014 11:46
Last modified: 18 Mar 2024 02:52
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Author:
A.J. Drake
Author:
R.C. McPherson
Author:
R.R. Meehan
Author:
J Seckl
Author:
R.M. Reynolds
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