Maternal nutrition at conception modulates DNA methylation of human metastable epialleles

Abstract

In experimental animals, maternal diet during the periconceptional period influences the establishment of DNA methylation at metastable epialleles in the offspring, with permanent phenotypic consequences. Pronounced naturally occurring seasonal differences in the diet of rural Gambian women allowed us to test this in humans. We show that significant seasonal variations in methyl-donor nutrient intake of mothers around the time of conception influence 13 relevant plasma biomarkers. The level of several of these maternal biomarkers predicts increased/decreased methylation at metastable epialleles in DNA extracted from lymphocytes and hair follicles in infants postnatally. Our results demonstrate that maternal nutritional status during early pregnancy causes persistent and systemic epigenetic changes at human metastable epialleles.

Adolescence and the next generation

“…Of note are studies of metastable epialleles, epigenetically labile regions of the genome that are subject to large changes in response to environmental influences during very early embryogenesis. These regions were first described in mice, but subsequent human studies in Gambia have demonstrated epigenetic variation at metastable epialleles that are linked to periconceptional maternal nutrition 77 , findings that have later been replicated in a rural Bangladeshi cohort 78 . The methylation status of metastable epialleles has been linked to later obesity and metabolic function 79 .…”

Offspring DNA methylation of the aryl-hydrocarbon receptor repressor gene is associated with maternal BMI, gestational age, and birth weight

“…A very small proportion of individuals (65) from the end of cohort enrollment also had food-frequency data, allowing for adjustment for folic acid intake in a subset of the population because methyl donor intake might be associated with offspring DNA methylation. 47 We also re-analyzed our data excluding the one current smoker in our cohort.…”

Stat3 is a candidate epigenetic biomarker of perinatal Bisphenol A exposure associated with murine hepatic tumors with implications for human health

“…10 Other studies have demonstrated the presence of stochastic and global epigenomic changes following environmental exposures in mice 1,11 and humans. 12 In order to facilitate translation of animal studies that identify epigenetic biomarkers of environmental exposure and disease risk to human health and disease prevention, studies must demonstrate epigenetic changes not only at a single time point but across the life-course, and validate with mechanistic and epidemiological studies.…”