Metabolic stress induces modifications in the epigenetic program of preimplantation bovine embryos

Mol Reprod Dev. 2018 Feb;85(2):117-127. doi: 10.1002/mrd.22941. Epub 2018 Jan 17.

Abstract

The mammalian embryo is sensitive to and adapts to its metabolic environment. The mother's metabolic health and nutrient availability, for example, can modulate the oviductal fluid composition and thus embryo development. In this project, we induced energetic stress in bovine embryos during early culture to observe the epigenetic responses associated with metabolic stress, using a treatment paradigm known to decrease blastocyst rates. Embryos were generated using oocytes from slaughtered cows, and then exposed to an elevated glucose concentration (5 vs. 0.2 mM in control conditions) for the first 3 days post-fertilization, followed by normal media until the blastocyst stage. The EmbryoGENE platform was then used to identify DNA methylation differences between the two treatments. Probes (450,000) were then analyzed based on their genome location and methylation differences. Our results revealed that elevated glucose led to hypomethylation close to telomeric regions and methylation changes on genomic regions associated with energy metabolism.

Keywords: DNA methylation; embryo glucose; metabolic programming.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastocyst / drug effects
  • Blastocyst / metabolism*
  • Cattle* / embryology
  • Cattle* / genetics
  • Cells, Cultured
  • CpG Islands / drug effects
  • CpG Islands / genetics
  • DNA Methylation* / drug effects
  • Embryo Culture Techniques / veterinary
  • Embryo, Mammalian / drug effects
  • Embryonic Development / drug effects
  • Embryonic Development / physiology
  • Epigenesis, Genetic* / drug effects
  • Epigenesis, Genetic* / physiology
  • Female
  • Fertilization in Vitro / veterinary
  • Gene Expression Regulation, Developmental* / drug effects
  • Gene Expression Regulation, Developmental* / genetics
  • Glucose / pharmacology
  • Male
  • Stress, Physiological / physiology*

Substances

  • Glucose