TY - JOUR
T1 - Gestational diabetes alters offspring DNA methylation profiles in human and rat
T2 - Identification of key pathways involved in endocrine system disorders, insulin signaling, diabetes signaling, and ILK signaling
AU - Petropoulos, Sophie
AU - Guillemin, Claire
AU - Ergaz, Zivanit
AU - Dimov, Sergiy
AU - Suderman, Matthew
AU - Weinstein-Fudim, Liza
AU - Ornoy, Asher
AU - Szyf, Moshe
N1 - Publisher Copyright:
Copyright © 2015 by the Endocrine Society.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84929203519&partnerID=8YFLogxK
U2 - 10.1210/en.2014-1643
DO - 10.1210/en.2014-1643
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 25514087
AN - SCOPUS:84929203519
SN - 0013-7227
VL - 156
SP - 2222
EP - 2238
JO - Endocrinology
JF - Endocrinology
IS - 6
ER -