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Endocrinology. 2015 Jun;156(6):2222-38. doi: 10.1210/en.2014-1643. Epub 2014 Dec 16.

Gestational Diabetes Alters Offspring DNA Methylation Profiles in Human and Rat: Identification of Key Pathways Involved in Endocrine System Disorders, Insulin Signaling, Diabetes Signaling, and ILK Signaling.

Author information

1
Department of Pharmacology and Therapeutics (S.P., C.G., S.D., M.Su., M.Sz.) and Sackler Program for Epigenetics and Psychobiology (M.Sz.), McGill University, Montréal, Canada H3G 1Y6; and Laboratory of Teratology (Z.E., L.W.-F., A.O.), Department of Medical Neurobiology, Hebrew University-Haddassah Medical School, Jerusalem 91120, Israel.

Abstract

Gestational diabetes is associated with risk for metabolic disease later in life. Using a cross-species approach in rat and humans, we examined the hypothesis that gestational diabetes during pregnancy triggers changes in the methylome of the offspring that might be mediating these risks. We show in a gestation diabetes rat model, the Cohen diabetic rat, that gestational diabetes triggers wide alterations in DNA methylation in the placenta in both candidate diabetes genes and genome-wide promoters, thus providing evidence for a causal relationship between diabetes during pregnancy and DNA methylation alterations. There is a significant overlap between differentially methylated genes in the placenta and the liver of the rat offspring. Several genes differentially methylated in rat placenta exposed to maternal diabetes are also differentially methylated in the human placenta of offspring exposed to gestational diabetes in utero. DNA methylation changes inversely correlate with changes in expression. The changes in DNA methylation affect known functional gene pathways involved in endocrine function, metabolism, and insulin responses. These data provide support to the hypothesis that early-life exposures and their effects on metabolic disease are mediated by DNA methylation changes. This has important diagnostic and therapeutic implications.

PMID:
25514087
DOI:
10.1210/en.2014-1643
[Indexed for MEDLINE]

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