Gestational sleep apnea perturbations induce metabolic disorders by divergent epigenomic regulation

Epigenomics. 2021 May;13(10):751-765. doi: 10.2217/epi-2020-0435. Epub 2021 Apr 30.

Abstract

Aim: Late-gestational sleep fragmentation (LG-SF) and intermittent hypoxia (LG-IH), two hallmarks of obstructive sleep apnea, lead to metabolic dysfunction in the offspring. We investigated specific biological processes that are epigenetically regulated by LG-SF and LG-IH. Materials & methods: We analyzed DNA methylation profiles in offspring visceral white adipose tissues by MeDIP-chip followed by pathway analysis. Results: We detected 1187 differentially methylated loci (p < 0.01) between LG-SF and LG-IH. Epigenetically regulated genes in LG-SF offspring were associated with lipid and glucose metabolism, whereas those in LG-IH were related to inflammatory signaling and cell proliferation. Conclusion: While LG-SF and LG-IH will result in equivalent phenotypic alterations in offspring, each paradigm appears to operate through epigenetic regulation of different biological processes.

Keywords: DNA methylation; inflammation; intermittent hypoxia; late-gestation; lipid metabolism; metabolism; obstructive sleep apnea; oxidative stress; sleep fragmentation; visceral white adipose tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA Methylation
  • Epigenesis, Genetic
  • Epigenomics
  • Female
  • Hypoxia / genetics*
  • Intra-Abdominal Fat / metabolism
  • Metabolic Diseases / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Obesity / genetics
  • Phenotype
  • Pregnancy
  • Prenatal Exposure Delayed Effects / genetics*
  • Sleep Apnea Syndromes / genetics*