Dietary supplementation with polyunsaturated fatty acid during pregnancy modulates DNA methylation at IGF2/H19 imprinted genes and growth of infants

Abstract

I. Dietary supplementation with polyunsaturated fatty acid during pregnancy modulates DNA methylation at IGF2/H19 imprinted genes and growth of infants. Physiol Genomics 46: 851-857, 2014. First published October 7, 2014 doi:10.1152/physiolgenomics.00061.2014.-Epigenetic regulation of imprinted genes is regarded as a highly plausible explanation for linking dietary exposures in early life with the onset of diseases during childhood and adulthood. We sought to test whether prenatal dietary supplementation with docosahexaenoic acid (DHA) during pregnancy may modulate epigenetic states at birth. This study was based on a randomized intervention trial conducted in Mexican pregnant women supplemented daily with 400 mg of DHA or a placebo from gestation week 18 -22 to parturition. We applied quantitative profiling of DNA methylation states at IGF2 promoter 3 (IGF2 P3), IGF2 differentially methylated region (DMR), and H19 DMR in cord blood mononuclear cells of the DHA-supplemented group (n ϭ 131) and the control group (n ϭ 130). In stratified analyses, DNA methylation levels in IGF2 P3 were significantly higher in the DHA group than the control group in preterm infants (P ϭ 0.04). We also observed a positive association between DNA methylation levels and maternal body mass index; IGF2 DMR methylation was higher in the DHA group than the control group in infants of overweight mothers (P ϭ 0.03). In addition, at H19 DMR, methylation levels were significantly lower in the DHA group than the control group in infants of normal weight mothers (P ϭ 0.01). Finally, methylation levels at IGF2/H19 imprinted regions were associated with maternal BMI. These findings suggest that epigenetic mechanisms may be modulated by DHA, with potential impacts on child growth and development. epigenetics; DHA supplementation; pregnancy; imprinted genes; maternal BMI; IGF2; H19 EPIGENETIC MODIFICATIONS ARE thought to stabilize gene expression patterns in specific cell types and to play a role in the maintenance of cell identity and differentiation fates. However, epigenetic patterns are globally reconfigured when gametes fuse to form the zygote, and gamete precursors develop and migrate in the embryo (50). Epigenetic reprogramming occurs during normal embryonic and fetal development and differentiation and might be affected by environmental exposures, resulting in long-lasting changes that could affect health and the risk of diseases in later life (2). The critical window of vulnerability to relevant environmental exposures during epigenetic reprogramming is crucial to understand the full impact of these factors on health (7). Environmental exposures that affect epigenetic reprogramming and maintenance of cell identity have been documented, including in utero exposure to dietary micronutrients (31, 43), caloric restriction (10), protein restriction (8), and cigarette smoking (30). Therefore, epigenetic regulation is regarded as a highly plausible explanation for linking dietary exposures in utero and in early life with the onset of chronic dise...

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.…”

Cyp1b1 deletion and retinol deficiency coordinately suppress mouse liver lipogenic genes and hepcidin expression during post-natal development

“…Igf2 also shows very high perinatal expression with a similar acute post-natal decline. Expression of the major growth regulator, Igf2/H19 , is highly dependent on epigenetic modulation of methylation status (Lee et al, 2014). Each matched the cholesterol pathway signature with increases in Cyp1b1 deletion and insensitivity to GVAD, except in combination (Table 3).…”

Growth and Life Course Health Development

“…Among humans, epigenotypes are influenced by health states as illustrated by the association between impaired maternal glucose tolerance and decreased placental leptin gene expression induced by hypermethylation (Bouchard et al 2010). Likewise, epigenetic effects secondary to maternal dietary intake are a mechanistic source for variation in fetal and postnatal adiposity and growth (Lee et al 2014). …”