DNA methylation pattern of bovine blastocysts associated with hyperinsulinemia in vitro

Abstract

Insulin functions as a regulator of metabolism and plays an important role in reproduction. Hyperinsulinemia is often observed in patients with obesity and diabetes type 2 and is known to impair fertility, but the underlying molecular mechanisms are only partly understood. Metabolic programming through epigenetic mechanisms such as DNA methylation during embryonic development can lead to health implications for the offspring later in life. Our aim was to study the potential effect of hyperinsulinemia on gene expression and DNA methylation of embryos by adding insulin (0.1 mu g/ml=INS0.1 or 10 mu g/ml=INS10) during in vitro oocyte maturation by using the EmbryoGENE DNA methylation array for a study of the bovine epigenome. Our results showed significant differences between blastocysts originating from insulin-treated oocytes compared with untreated control blastocysts. In total, 13,658 and 12,418 probes were differentially methylated (DM) in INS0.1 and INS10, respectively, with an overlap of 3,233 probes in the DM regions (DMR) for both insulin groups. Genes related to pathways such as lipid metabolism, growth and proliferation, mitochondrial function, and oxidative stress responses were influenced at both the epigenetic and transcriptomic levels. In addition, imprinted genes and genes with functions in the epigenetic machinery were among the DMRs. This study identified DMRs correlated to differential expression of genes involved in metabolic regulation and should help to improve our knowledge of the underlying molecular mechanisms of metabolic imbalance.

Keywords

diabetes type 2; hyperinsulinemia; metabolic imbalance; metabolic programming; oocyte maturation

Published in

Molecular Reproduction and Development
2018, volume: 85, number: 7, pages: 599-611
Publisher: WILEY

SLU Authors

• Laskowski, Denise

  • Department of Clinical Sciences, Swedish University of Agricultural Sciences
    

• Humblot, Patrice

  • Department of Clinical Sciences, Swedish University of Agricultural Sciences
    

• Sjunnesson, Ylva

  • Department of Clinical Sciences, Swedish University of Agricultural Sciences
    

• Jhamat, Naveed

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

• Båge, Renee

  • Department of Clinical Sciences, Swedish University of Agricultural Sciences
    

• Andersson, Göran

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

Global goals (SDG)

SDG3 Good health and well-being

UKÄ Subject classification

Clinical Science
Animal and Dairy Science
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Publication identifier

• DOI: https://doi.org/10.1002/mrd.22995

Permanent link to this page (URI)

https://res.slu.se/id/publ/96513