The effect of paternal methyl-group donor intake on offspring DNA methylation and birth weight

J Dev Orig Health Dis. 2017 Jun;8(3):311-321. doi: 10.1017/S2040174417000046. Epub 2017 Mar 6.

Abstract

Most nutritional studies on the development of children focus on mother-infant interactions. Maternal nutrition is critically involved in the growth and development of the fetus, but what about the father? The aim is to investigate the effects of paternal methyl-group donor intake (methionine, folate, betaine, choline) on paternal and offspring global DNA (hydroxy)methylation, offspring IGF2 DMR DNA methylation, and birth weight. Questionnaires, 7-day estimated dietary records, whole blood samples, and anthropometric measurements from 74 fathers were obtained. A total of 51 cord blood samples were collected and birth weight was obtained. DNA methylation status was measured using liquid chromatography-tandem mass spectrometry (global DNA (hydroxy)methylation) and pyrosequencing (IGF2 DMR methylation). Paternal betaine intake was positively associated with paternal global DNA hydroxymethylation (0.028% per 100 mg betaine increase, 95% CI: 0.003, 0.053, P=0.03) and cord blood global DNA methylation (0.679% per 100 mg betaine increase, 95% CI: 0.057, 1.302, P=0.03). Paternal methionine intake was positively associated with CpG1 (0.336% per 100 mg methionine increase, 95% CI: 0.103, 0.569, P=0.006), and mean CpG (0.201% per 100 mg methionine increase, 95% CI: 0.001, 0.402, P=0.049) methylation of the IGF2 DMR in cord blood. Further, a negative association between birth weight/birth weight-for-gestational age z-score and paternal betaine/methionine intake was found. In addition, a positive association between choline and birth weight/birth weight-for-gestational age z-score was also observed. Our data indicate a potential impact of paternal methyl-group donor intake on paternal global DNA hydroxymethylation, offspring global and IGF2 DMR DNA methylation, and prenatal growth.

Keywords: IGF2 DMR methylation; global DNA hydroxymethylation; global DNA methylation; methyl-group donor.

MeSH terms

  • Adult
  • Belgium / epidemiology
  • Betaine / administration & dosage*
  • Betaine / blood
  • Birth Weight / physiology*
  • Choline / administration & dosage*
  • Choline / blood
  • DNA Methylation / physiology*
  • Female
  • Fetal Blood / metabolism
  • Folic Acid / administration & dosage*
  • Folic Acid / blood
  • Humans
  • Male
  • Methionine / administration & dosage*
  • Methionine / blood
  • Middle Aged
  • Obesity / blood
  • Obesity / epidemiology

Substances

  • Betaine
  • Folic Acid
  • Methionine
  • Choline