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
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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. / Manitta, Eleonora; Marques, Irene Carolina Fontes; Bredgaard, Sandra Stokholm; Kelstrup, Louise; Houshmand-Oeregaard, Azadeh; Clausen, Tine Dalsgaard; Grunnet, Louise Groth; Mathiesen, Elisabeth Reinhardt; Dalgaard, Louise Torp; Barrès, Romain; Vaag, Allan Arthur; Damm, Peter; Hjort, Line.
I: Biomedicines, Bind 10, Nr. 6, 1244, 2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - 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
AU - Manitta, Eleonora
AU - Marques, Irene Carolina Fontes
AU - Bredgaard, Sandra Stokholm
AU - Kelstrup, Louise
AU - Houshmand-Oeregaard, Azadeh
AU - Clausen, Tine Dalsgaard
AU - Grunnet, Louise Groth
AU - Mathiesen, Elisabeth Reinhardt
AU - Dalgaard, Louise Torp
AU - Barrès, Romain
AU - Vaag, Allan Arthur
AU - Damm, Peter
AU - Hjort, Line
N1 - Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - adipose tissue
KW - developmental programming
KW - DNA methylation
KW - epigenetics
KW - ESM1
KW - gene expression
KW - gestational diabetes
KW - intrauterine hyperglycemia
KW - MS4A3
KW - TSPAN14
KW - type 1 diabetes
U2 - 10.3390/biomedicines10061244
DO - 10.3390/biomedicines10061244
M3 - Journal article
C2 - 35740266
AN - SCOPUS:85131597756
VL - 10
JO - Biomedicines
JF - Biomedicines
SN - 2227-9059
IS - 6
M1 - 1244
ER -
ID: 314440314