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Abstract
Offspring exposed to gestational diabetes mellitus (GDM) have an increased risk for chronic diseases, and one promising mechanism for fetal metabolic programming is epigenetics. Therefore, we postulated that GDM exposure impacts the offspring’s methylome and used an epigenomic approach to explore this hypothesis. Placenta and cord blood samples were obtained from 44 newborns, including 30 exposed to GDM. Women were recruited at first trimester of pregnancy and followed until delivery. GDM was assessed after a 75-g oral glucose tolerance test at 24–28 weeks of pregnancy. DNA methylation was measured at > 485,000 CpG sites (Infinium HumanMethylation450 BeadChips). Ingenuity Pathway Analysis was conducted to identify metabolic pathways epigenetically affected by GDM. Our results showed that 3,271 and 3,758 genes in placenta and cord blood, respectively, were potentially differentially methylated between samples exposed or not to GDM (p-values down to 1 × 10−06; none reached the genome-wide significance levels), with more than 25% (n = 1,029) being common to both tissues. Mean DNA methylation differences between groups were 5.7 ± 3.2% and 3.4 ± 1.9% for placenta and cord blood, respectively. These genes were likely involved in the metabolic diseases pathway (up to 115 genes (11%), p-values for pathways = 1.9 × 10−13 < p < 4.0 × 10−03; including diabetes mellitus p = 4.3 × 10−11). Among the differentially methylated genes, 326 in placenta and 117 in cord blood were also associated with newborn weight. Our results therefore suggest that GDM has epigenetic effects on genes preferentially involved in the metabolic diseases pathway, with consequences on fetal growth and development, and provide supportive evidence that DNA methylation is involved in fetal metabolic programming.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
This project was supported by ECOGENE-21, the Canadian Institutes of Health Research (CIHR team in community genetics [grant #CTP-82941]), the CIHR and Fonds de la Recherche du Québec, Santé (FRQ-S). SMR is recipient of a postdoctoral fellowship from the Canadian Diabetes Association. AAH is a recipient of a scholarship from Diabète Québec, the Faculty of Medicine and Health Sciences, Université de Sherbrooke and the FRQ-S. LB and MFH are junior research scholars from the FRQ-S. MFH is also supported by a Canadian Diabetes Association clinical scientist award. LB, MFH, PP and JPB are members of the FRQ-S-funded Centre de recherche clinique Étienne-Le Bel (affiliated to Centre Hospitalier de l’Université de Sherbrooke).
We warmly acknowledge the contribution of Sébastien Claveau (MSc), ECOGENE-21 Laboratory; Nadia Mior, ECOGENE-21 Laboratory; Jeannine Landry (RN), ECOGENE-21 Clinical Research Center; and Chantale Aubut (RN), ECOGENE-21 Clinical Research Center for their dedicated work in this study. We also express our gratitude to Céline Bélanger, Chicoutimi Hospital, for her thoughtful revision of the manuscript.
Authors Contributions
SMR and AAH performed the data analysis and interpretation and wrote the manuscript. GV performed the data analysis and revised the manuscript. JSP, JPB, DG revised the manuscript. MFH contributed to discussions and revised the manuscript. PP and DB participated in the conception of the study design and revised the manuscript. LB conceived the study design, participated in the data interpretation, contributed to discussions and revised the manuscript.
Supplemental Materials
Supplemental materials may be found here: http://www.landesbioscience.com/journals/epigenetics/article/25578/