In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism

Adverse prenatal environments can promote metabolic disease in offspring and subsequent generations. Animal models and epidemiological data implicate epigenetic inheritance, but the mechanisms remain unknown. In an intergenerational developmental programming model affecting F2 mouse metabolism, we demonstrate that the in utero nutritional environment of F1 embryos alters the germline DNA methylome of F1 adult males in a locus-specific manner. Differentially methylated regions are hypomethylated and enriched in nucleosome-retaining regions. A substantial fraction is resistant to early embryo methylation reprogramming, which may have an impact on F2 development. Differential methylation is not maintained in F2…

• MR
  Medical Research Council

  Award: MR/J001597/1
• BA
  Biotechnology and Biological Sciences Research Council

  Awards: BBS/E/B/000C0402, BBS/E/B/0000S266