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The role of maternal DNA methylation in pregnancies complicated by gestational diabetes

Diabetes in pregnancy is associated with adverse pregnancy outcomes and poses a serious threat to the health of mother and child. Although the pathophysiological mechanisms that underlie the association between maternal diabetes and pregnancy complications have not yet been elucidated, it has been s...

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Autores principales: Dias, Stephanie, Willmer, Tarryn, Adam, Sumaiya, Pheiffer, Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10012132/
https://www.ncbi.nlm.nih.gov/pubmed/36992770
http://dx.doi.org/10.3389/fcdhc.2022.982665
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author Dias, Stephanie
Willmer, Tarryn
Adam, Sumaiya
Pheiffer, Carmen
author_facet Dias, Stephanie
Willmer, Tarryn
Adam, Sumaiya
Pheiffer, Carmen
author_sort Dias, Stephanie
collection PubMed
description Diabetes in pregnancy is associated with adverse pregnancy outcomes and poses a serious threat to the health of mother and child. Although the pathophysiological mechanisms that underlie the association between maternal diabetes and pregnancy complications have not yet been elucidated, it has been suggested that the frequency and severity of pregnancy complications are linked to the degree of hyperglycemia. Epigenetic mechanisms reflect gene-environment interactions and have emerged as key players in metabolic adaptation to pregnancy and the development of complications. DNA methylation, the best characterized epigenetic mechanism, has been reported to be dysregulated during various pregnancy complications, including pre-eclampsia, hypertension, diabetes, early pregnancy loss and preterm birth. The identification of altered DNA methylation patterns may serve to elucidate the pathophysiological mechanisms that underlie the different types of maternal diabetes during pregnancy. This review aims to provide a summary of existing knowledge on DNA methylation patterns in pregnancies complicated by pregestational type 1 (T1DM) and type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM). Four databases, CINAHL, Scopus, PubMed and Google Scholar, were searched for studies on DNA methylation profiling in pregnancies complicated with diabetes. A total of 1985 articles were identified, of which 32 met the inclusion criteria and are included in this review. All studies profiled DNA methylation during GDM or impaired glucose tolerance (IGT), while no studies investigated T1DM or T2DM. We highlight the increased methylation of two genes, Hypoxia‐inducible Factor‐3α (HIF3α) and Peroxisome Proliferator-activated Receptor Gamma-coactivator-Alpha (PGC1-α), and the decreased methylation of one gene, Peroxisome Proliferator Activated Receptor Alpha (PPARα), in women with GDM compared to pregnant women with normoglycemia that were consistently methylated across diverse populations with varying pregnancy durations, and using different diagnostic criteria, methodologies and biological sources. These findings support the candidacy of these three differentially methylated genes as biomarkers for GDM. Furthermore, these genes may provide insight into the pathways that are epigenetically influenced during maternal diabetes and which should be prioritized and replicated in longitudinal studies and in larger populations to ensure their clinical applicability. Finally, we discuss the challenges and limitations of DNA methylation analysis, and the need for DNA methylation profiling to be conducted in different types of maternal diabetes in pregnancy.
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spelling pubmed-100121322023-03-28 The role of maternal DNA methylation in pregnancies complicated by gestational diabetes Dias, Stephanie Willmer, Tarryn Adam, Sumaiya Pheiffer, Carmen Front Clin Diabetes Healthc Clinical Diabetes and Healthcare Diabetes in pregnancy is associated with adverse pregnancy outcomes and poses a serious threat to the health of mother and child. Although the pathophysiological mechanisms that underlie the association between maternal diabetes and pregnancy complications have not yet been elucidated, it has been suggested that the frequency and severity of pregnancy complications are linked to the degree of hyperglycemia. Epigenetic mechanisms reflect gene-environment interactions and have emerged as key players in metabolic adaptation to pregnancy and the development of complications. DNA methylation, the best characterized epigenetic mechanism, has been reported to be dysregulated during various pregnancy complications, including pre-eclampsia, hypertension, diabetes, early pregnancy loss and preterm birth. The identification of altered DNA methylation patterns may serve to elucidate the pathophysiological mechanisms that underlie the different types of maternal diabetes during pregnancy. This review aims to provide a summary of existing knowledge on DNA methylation patterns in pregnancies complicated by pregestational type 1 (T1DM) and type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM). Four databases, CINAHL, Scopus, PubMed and Google Scholar, were searched for studies on DNA methylation profiling in pregnancies complicated with diabetes. A total of 1985 articles were identified, of which 32 met the inclusion criteria and are included in this review. All studies profiled DNA methylation during GDM or impaired glucose tolerance (IGT), while no studies investigated T1DM or T2DM. We highlight the increased methylation of two genes, Hypoxia‐inducible Factor‐3α (HIF3α) and Peroxisome Proliferator-activated Receptor Gamma-coactivator-Alpha (PGC1-α), and the decreased methylation of one gene, Peroxisome Proliferator Activated Receptor Alpha (PPARα), in women with GDM compared to pregnant women with normoglycemia that were consistently methylated across diverse populations with varying pregnancy durations, and using different diagnostic criteria, methodologies and biological sources. These findings support the candidacy of these three differentially methylated genes as biomarkers for GDM. Furthermore, these genes may provide insight into the pathways that are epigenetically influenced during maternal diabetes and which should be prioritized and replicated in longitudinal studies and in larger populations to ensure their clinical applicability. Finally, we discuss the challenges and limitations of DNA methylation analysis, and the need for DNA methylation profiling to be conducted in different types of maternal diabetes in pregnancy. Frontiers Media S.A. 2022-09-21 /pmc/articles/PMC10012132/ /pubmed/36992770 http://dx.doi.org/10.3389/fcdhc.2022.982665 Text en Copyright © 2022 Dias, Willmer, Adam and Pheiffer https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Clinical Diabetes and Healthcare
Dias, Stephanie
Willmer, Tarryn
Adam, Sumaiya
Pheiffer, Carmen
The role of maternal DNA methylation in pregnancies complicated by gestational diabetes
title The role of maternal DNA methylation in pregnancies complicated by gestational diabetes
title_full The role of maternal DNA methylation in pregnancies complicated by gestational diabetes
title_fullStr The role of maternal DNA methylation in pregnancies complicated by gestational diabetes
title_full_unstemmed The role of maternal DNA methylation in pregnancies complicated by gestational diabetes
title_short The role of maternal DNA methylation in pregnancies complicated by gestational diabetes
title_sort role of maternal dna methylation in pregnancies complicated by gestational diabetes
topic Clinical Diabetes and Healthcare
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10012132/
https://www.ncbi.nlm.nih.gov/pubmed/36992770
http://dx.doi.org/10.3389/fcdhc.2022.982665
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