AUTHOR=Dias Stephanie , Willmer Tarryn , Adam Sumaiya , Pheiffer Carmen 

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

JOURNAL=Frontiers in Clinical Diabetes and Healthcare

VOLUME=Volume 3 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/clinical-diabetes-and-healthcare/articles/10.3389/fcdhc.2022.982665

DOI=10.3389/fcdhc.2022.982665

ISSN=2673-6616

ABSTRACT=Pregestational type 1 (T1DM), and type 2 diabetes mellitus (T2DM) are associated with more frequent and severe adverse outcomes than gestational diabetes mellitus (GDM), although the pathophysiological mechanisms that underlie the association between maternal diabetes type and pregnancy complications have not yet been elucidated. 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, GDM, 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 T1DM, T2DM, and 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 (HIF3A) 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 controls, that were similar in two or more studies, in different populations, across different gestational ages and using different biological sources such as omental tissue, placenta and cord blood at delivery. These findings support the candidacy of these three differentially methylated genes as biomarkers for GDM. These genes may provide insight into the pathways that are epigenetically influenced during diabetes in pregnancy, which may be related to pregnancy outcomes and should be prioritized and replicated in larger populations in future studies. 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.