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


METHODS
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.


METHODS
DNA methylation at 11β-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.
Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Amanda J
AJ
Drake
Rhoanne C
RC
McPherson
Keith M
KM
Godfrey
Cyrus
C
Cooper
Karen A
KA
Lillycrop
Mark A
MA
Hanson
Richard R
RR
Meehan
Jonathan R
JR
Seckl
Rebecca M
RM
Reynolds
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics; D000328:Adult; D000886:Anthropometry; D001724:Birth Weight; D001794:Blood Pressure / Q000235:genetics; D004247:DNA / Q000097:blood; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D047109:Fetal Development / Q000235:genetics*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000235:genetics; D007231:Infant, Newborn; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D039382:Maternal Nutritional Physiological Phenomena / Q000235:genetics*; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011965:Receptors, Glucocorticoid / Q000235:genetics
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D007335:Insulin-Like Growth Factor II; D004247:DNA; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D006854:Hydrocortisone