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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

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 adole...

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Autores principales: Manitta, Eleonora, Fontes Marques, Irene Carolina, Stokholm Bredgaard, Sandra, Kelstrup, Louise, Houshmand-Oeregaard, Azadeh, Dalsgaard Clausen, Tine, Groth Grunnet, Louise, Reinhardt Mathiesen, Elisabeth, Torp Dalgaard, Louise, Barrès, Romain, Vaag, Allan Arthur, Damm, Peter, Hjort, Line
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219870/
https://www.ncbi.nlm.nih.gov/pubmed/35740266
http://dx.doi.org/10.3390/biomedicines10061244
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author Manitta, Eleonora
Fontes Marques, Irene Carolina
Stokholm Bredgaard, Sandra
Kelstrup, Louise
Houshmand-Oeregaard, Azadeh
Dalsgaard Clausen, Tine
Groth Grunnet, Louise
Reinhardt Mathiesen, Elisabeth
Torp Dalgaard, Louise
Barrès, Romain
Vaag, Allan Arthur
Damm, Peter
Hjort, Line
author_facet Manitta, Eleonora
Fontes Marques, Irene Carolina
Stokholm Bredgaard, Sandra
Kelstrup, Louise
Houshmand-Oeregaard, Azadeh
Dalsgaard Clausen, Tine
Groth Grunnet, Louise
Reinhardt Mathiesen, Elisabeth
Torp Dalgaard, Louise
Barrès, Romain
Vaag, Allan Arthur
Damm, Peter
Hjort, Line
author_sort Manitta, Eleonora
collection PubMed
description 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.
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spelling pubmed-92198702022-06-24 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 Fontes Marques, Irene Carolina Stokholm Bredgaard, Sandra Kelstrup, Louise Houshmand-Oeregaard, Azadeh Dalsgaard Clausen, Tine Groth Grunnet, Louise Reinhardt Mathiesen, Elisabeth Torp Dalgaard, Louise Barrès, Romain Vaag, Allan Arthur Damm, Peter Hjort, Line Biomedicines Article 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. MDPI 2022-05-26 /pmc/articles/PMC9219870/ /pubmed/35740266 http://dx.doi.org/10.3390/biomedicines10061244 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Manitta, Eleonora
Fontes Marques, Irene Carolina
Stokholm Bredgaard, Sandra
Kelstrup, Louise
Houshmand-Oeregaard, Azadeh
Dalsgaard Clausen, Tine
Groth Grunnet, Louise
Reinhardt Mathiesen, Elisabeth
Torp Dalgaard, Louise
Barrès, Romain
Vaag, Allan Arthur
Damm, Peter
Hjort, Line
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219870/
https://www.ncbi.nlm.nih.gov/pubmed/35740266
http://dx.doi.org/10.3390/biomedicines10061244
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