Gestational sleep apnea perturbations induce metabolic disorders by divergent epigenomic regulation.

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.