ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2010) 24 OC2.2

An unbalanced maternal diet in pregnancy is associated with epigenetic effects in the offspring

A Drake, R Knox, J Seckl & R Reynolds

University of Edinburgh, Edinburgh, UK.

Epigenetic dysregulation may be one mechanism underpinning the link between early life conditions and later cardiometabolic risk. In animal models, environmental manipulations including modified maternal diet change DNA methylation and offspring phenotype. Manipulations altering the epigenetic state reverse the phenotype suggesting causality. We have previously reported higher blood pressure (BP) and cortisol in an adult cohort whose mothers were advised to eat a high-protein, low-carbohydrate diet during pregnancy. Here we investigated the hypothesis that this unbalanced maternal diet alters DNA methylation at genes important in growth (insulin-like growth factor, IGF2) and glucocorticoid signalling (glucocorticoid receptor, GR; 11β hydroxysteroid dehydrogenase type 2, HSD2).

Height, weight, waist circumference and BP were measured in 34 individuals (mean age 40y) for whom maternal diet and birth parameters were known. DNA was extracted from peripheral blood mononuclear cells and pyrosequencing used to measure DNA methylation at the differentially methylated regions of IGF2 and the promoters of GR and HSD2.

In univariate analyses, there was an inverse relationship between birth length and IGF2 methylation and a positive correlation between HSD2 methylation and birthweight. These findings remained significant in regression analyses. Methylation at IGF2 and HSD2 were also significantly positively associated with adult anthropometry including weight, waist circumference, BMI and BP. In exploratory analyses of maternal diet, methylation at GR and HSD2 was significantly higher in those whose mothers followed specific dietary advice to increase protein and reduce carbohydrateintake.

Thus, methylation at key genes regulating fetal growth, BP and glucocorticoid signalling is associated with early life parameters and adult cardiometabolic risk factors. Additionally, maternal diet impacts on DNA methylation at genes involved in BP and HPA axis regulation. These results suggest epigenetic modifications play an important role in the early life programming of adult disease risk and that this may be estimated in accessible leucocyte DNA.

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