Seasons influence the methylation profiles of newborns: more evidence that mom’s diet during pregnancy has lasting effects in her offspring.
Metastable epialleles (ME) are gene alleles that are differentially expressed through epigenetic regulatory mechanisms. The DNA methylation status of an ME is established during embryonic development, and can be maintained later into life. The differential methylation of these MEs contribute to phenotypic diversity between individuals and provides an explanation for the epigenetic variability observed in monozygotic twins. In laboratory animals, studies have shown that maternal dietary intake strongly influences ME epigenetic status. Increased dietary exposure to a methyl-donor prior to, and during pregnancy, leads to hypermethylation at MEs and permanent phenotypic variance. In humans however, it has been challenging to elucidate the potential influence of maternal methyl-donor intake on ME methylation level due to methodological difficulties in precise dietary control in pre-gestational women.
Recently, Hennig et al presented an elegant study that documented seasonal fluctuations in maternal nutrient levels and correlated the data with infant ME status. The study was conducted in rural Gambia, where large seasonal nutrient variations exist due to only a single rainy season during the year and the dietary reliance on self-grown produce. Plasma levels of key methyl-donor molecules from an indicator group of 30 non-pregnant women were carefully measured over the course of a year to establish the seasonality of nutrient levels.
Once nutrient levels were established, a large group of 2040 women were routinely visited, until a missed menses occurred – suggesting pregnancy. Plasma biomarker levels were then measured and the pregnancy was confirmed one month later. Biomarker levels at gestation were extrapolated based on the indicator group. Maternal periconceptional concentrations of folate (FOL), vitamin B2, methionine (MET), and betaine (BET) were higher in the rainy season, and concentrations of active vitamin B12, dimethyl glycine (DMG), homocysteine (HCY) and S-adenosylhomocysteine (SAH) were lower. These measurements confirmed that maternal methyl-donor levels vary in a predictable, seasonal pattern. Offspring DNA methylation at MEs were later investigated in peripheral blood lymphocytes and hair follicle samples after birth. Infants born during the rainy season were found to have significantly higher levels of DNA methylation and an increase in maternal perigestational plasma levels of HCY and CYS correlated with decreased DNA methylation in offsprings! They also found that an increase in maternal vitamin B2 was predictive of an increase in offspring DNA methylation.
This study demonstrates for the first time, in human subjects, that maternal diet intake at gestation has long lasting effects on the epigome of the offspring! Unfortunately, the study was not able to provide further insights on the overall fitness of infants born in different season or the duration of the maternal diet-induced ME methylation. Future investigations addressing these questions is likely to deepen the current understanding on mechanisms of epigenetics as well as possess a substantial socioeconomic impact on the general public.
Source: Hennig BJ et al. Maternal nutrition at conception modulates DNA methylation of human metastable epialleles. Nat Commun. 2014 Apr 29;5:3746. doi: 10.1038/ncomms4746. PMCID: PMC4015319