Newborns of obese parents have altered DNA methylation patterns at imprinted genes

Abstract

BACKGROUND Several epidemiologic studies have demonstrated associations between periconceptional environmental exposures and health status of the offspring in later life. Although these environmentally related effects have been attributed to epigenetic changes, such as DNA methylation shifts at imprinted genes, little is known about the potential effects of maternal and paternal preconceptional overnutrition or obesity. OBJECTIVE We examined parental preconceptional obesity in relation to DNA methylation profiles at multiple human imprinted genes important in normal growth and development, such as: maternally expressed gene 3 (MEG3), mesoderm-specific transcript (MEST), paternally expressed gene 3 (PEG3), pleiomorphic adenoma gene-like 1 (PLAGL1), epsilon sarcoglycan and paternally expressed gene 10 (SGCE/PEG10) and neuronatin (NNAT). METHODS We measured methylation percentages at the differentially methylated regions (DMRs) by bisulfite pyrosequencing in DNA extracted from umbilical cord blood leukocytes of 92 newborns. Preconceptional obesity, defined as BMI ≥30 kg m−2, was ascertained through standardized questionnaires. RESULTS After adjusting for potential confounders and cluster effects, paternal obesity was significantly associated with lower methylation levels at the MEST (β = −2.57; s.e. =0.95; P =0.008), PEG3 (β = −1.71; s.e. =0.61; P =0.005) and NNAT (β = −3.59; s.e. =1.76; P =0.04) DMRs. Changes related to maternal obesity detected at other loci were as follows: β-coefficient was +2.58 (s.e. =1.00; P =0.01) at the PLAGL1 DMR and −3.42 (s.e. =1.69; P =0.04) at the MEG3 DMR. CONCLUSION We found altered methylation outcomes at multiple imprint regulatory regions in children born to obese parents, compared with children born to non-obese parents. In spite of the small sample size, our data suggest a preconceptional influence of parental life-style or overnutrition on the (re)programming of imprint marks during gametogenesis and early development. More specifically, the significant and independent association between paternal obesity and the offspring’s methylation status suggests the susceptibility of the developing sperm for environmental insults. The acquired imprint instability may be carried onto the next generation and increase the risk for chronic diseases in adulthood.

Prenatal Diet and Childhood ADHD: Exploring the Potential Role of IGF2 Methylation

“…This finding is consistent with previous research reporting an association between variation in offspring IGF2 methylation and prenatal dietary exposures, including periconceptional dietary supplementation (e.g. folic acid [15,16]; docosahexaenoic acid [17]), severe caloric restriction resulting from prenatal famine exposure [18], maternal obesity and BMI [17,19], as well as animal research on high-fat diet exposure [20]. The use of a prospective design additionally enabled us to examine longitudinal inter-relationships between unhealthy diet and IGF2 methylation, spanning gestation to mid-childhood.…”

Female offspring sired by diet induced obese male mice display impaired blastocyst development with molecular alterations to their ovaries, oocytes and cumulus cells

“…There are three potential explanations for the observed impaired reproductive health in these female offspring. Firstly, there may be a paternal transmission of impaired fertility due to epigenetic modifications in sperm as a result of their father's consumption of a HFD [15,[56][57][58]. Secondly, a paternal HFD may have initiated metabolic disturbances in offspring (impaired glucose tolerance and insulin sensitivity), which may cause the subfertility reported here.…”

Fruit intake and obesity Fruit and vegetables consumption and obesity in Brazil

“…When this condition develops in childhood there is a high possibility of it continuing in adult life 1 ; and obese parents raise children prone to the same condition, given the infl uence and interference of behavioural epigenetics, that modulates foetal metabolism from pregnancy 1,3 . Such relationships demonstrate the cyclical relationship of overweight and suggest the urgency and specifi city of therapeutic and preventive actions 4 .…”