DNA Methylation and Gene Expression in Blood and Adipose Tissue of Adult Offspring of Women with Diabetes in Pregnancy—A Validation Study of DNA Methylation Changes Identified in Adolescent Offspring
Eleonora Manitta,
Irene Carolina Fontes Marques,
Sandra Stokholm Bredgaard,
Louise Kelstrup,
Azadeh Houshmand-Oeregaard,
Tine Dalsgaard Clausen,
Louise Groth Grunnet,
Elisabeth Reinhardt Mathiesen,
Louise Torp Dalgaard,
Romain Barrès,
Allan Arthur Vaag,
Peter Damm,
Line Hjort
Affiliations
Eleonora Manitta
Novo Nordisk Foundation Center for Basic Metabolic Research, Metabolic Epigenetics Group, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Irene Carolina Fontes Marques
Department of Obstetrics, Center for Pregnant Women with Diabetes, Rigshospitalet, 2100 Copenhagen, Denmark
Sandra Stokholm Bredgaard
Department of Science and Environment, Roskilde University, 4000 Roskilde, Denmark
Louise Kelstrup
Department of Obstetrics, Center for Pregnant Women with Diabetes, Rigshospitalet, 2100 Copenhagen, Denmark
Azadeh Houshmand-Oeregaard
Department of Obstetrics, Center for Pregnant Women with Diabetes, Rigshospitalet, 2100 Copenhagen, Denmark
Tine Dalsgaard Clausen
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Louise Groth Grunnet
Steno Diabetes Center Copenhagen, Herlev Hospital, 2730 Herlev, Denmark
Elisabeth Reinhardt Mathiesen
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Louise Torp Dalgaard
Department of Science and Environment, Roskilde University, 4000 Roskilde, Denmark
Romain Barrès
Novo Nordisk Foundation Center for Basic Metabolic Research, Metabolic Epigenetics Group, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Allan Arthur Vaag
Steno Diabetes Center Copenhagen, Herlev Hospital, 2730 Herlev, Denmark
Peter Damm
Department of Obstetrics, Center for Pregnant Women with Diabetes, Rigshospitalet, 2100 Copenhagen, Denmark
Line Hjort
Novo Nordisk Foundation Center for Basic Metabolic Research, Metabolic Epigenetics Group, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Maternal gestational diabetes and obesity are associated with adverse outcomes in offspring, including increased risk of diabetes and cardiovascular diseases. Previously, we identified a lower DNA methylation degree at genomic sites near the genes ESM1, MS4A3, and TSPAN14 in the blood cells of adolescent offspring exposed to gestational diabetes and/or maternal obesity in utero. In the present study, we aimed to investigate if altered methylation and expression of these genes were detectable in blood, as well in the metabolically relevant subcutaneous adipose tissue, in a separate cohort of adult offspring exposed to gestational diabetes and obesity (O-GDM) or type 1 diabetes (O-T1D) in utero, compared with the offspring of women from the background population (O-BP). We did not replicate the findings of lower methylation of ESM1, MS4A3, and TSPAN14 in blood from adults, either in O-GDM or O-T1D. In contrast, in adipose tissue of O-T1D, we found higher MS4A3 DNA methylation, which will require further validation. The adipose tissue ESM1 expression was lower in O-GDM compared to O-BP, which in turn was not associated with maternal pre-pregnancy BMI nor the offspring’s own adiposity. Adipose tissue TSPAN14 expression was slightly lower in O-GDM compared with O-BP, but also positively associated with maternal pre-pregnancy BMI, as well as offspring’s own adiposity and HbA1c levels. In conclusion, the lower DNA methylation in blood from adolescent offspring exposed to GDM could not be confirmed in the present cohort of adult offspring, potentially due to methylation remodeling with increased aging. In offspring adipose tissue, ESM1 expression was associated with maternal GDM, and TSPAN14 expression was associated with both maternal GDM, as well as pre-pregnancy BMI. These altered expression patterns are potentially relevant to the concept of developmental programming of cardiometabolic diseases and require further studies.
