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An unbalanced maternal diet in pregnancy associates with offspring epigenetic changes in genes controlling glucocorticoid action and fetal growth

An unbalanced maternal diet in pregnancy associates with offspring epigenetic changes in genes controlling glucocorticoid action and fetal growth
An unbalanced maternal 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, Amanda J.
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McPherson, Rhoanne C.
d113a193-ee50-4102-abde-ad772570ac5f
Godfrey, Keith M.
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Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Meehan, Richard R.
d1eb907b-fe6c-43da-b6c2-df2b5569a536
Seckl, Jonathan R.
e82c92fd-cc5e-4428-bd06-a96991be61e3
Reynolds, Rebecca M.
0e42554c-fafd-447c-99ec-19b024c47302
Drake, Amanda J.
b27bb17b-6cfc-4e60-b0f3-df77f09371ce
McPherson, Rhoanne C.
d113a193-ee50-4102-abde-ad772570ac5f
Godfrey, Keith M.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Meehan, Richard R.
d1eb907b-fe6c-43da-b6c2-df2b5569a536
Seckl, Jonathan R.
e82c92fd-cc5e-4428-bd06-a96991be61e3
Reynolds, Rebecca M.
0e42554c-fafd-447c-99ec-19b024c47302

Drake, Amanda J., McPherson, Rhoanne C., Godfrey, Keith M., Cooper, Cyrus, Lillycrop, Karen A., Hanson, Mark A., Meehan, Richard R., Seckl, Jonathan R. and Reynolds, Rebecca M. (2012) An unbalanced maternal diet in pregnancy associates with offspring epigenetic changes in genes controlling glucocorticoid action and fetal growth. Clinical Endocrinology, 77 (6), 808-815.

Record type: Article

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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More information

e-pub ahead of print date: 9 November 2012
Published date: December 2012
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 347565
URI: http://eprints.soton.ac.uk/id/eprint/347565
PURE UUID: 7f476af8-563a-48ff-9625-858ba021c8eb
ORCID for Keith M. Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for Karen A. Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for Mark A. Hanson: ORCID iD orcid.org/0000-0002-6907-613X

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Date deposited: 25 Jan 2013 15:36
Last modified: 18 Mar 2024 02:52

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Contributors

Author: Amanda J. Drake
Author: Rhoanne C. McPherson
Author: Cyrus Cooper ORCID iD
Author: Mark A. Hanson ORCID iD
Author: Richard R. Meehan
Author: Jonathan R. Seckl
Author: Rebecca M. Reynolds

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