Epigenetic Changes in Gestational Diabetes Mellitus

Dłuski, Dominik; Wolińska, Ewa; Skrzypczak, Maciej

doi:10.3390/ijms22147649

Cited by 35 publications

(21 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Multiple studies in humans and animal models have shown that maternal obesity and GDM induce global and gene-specific DNA methylation changes in the placenta and other fetal tissues [ 13 , 14 ], which may contribute to the mechanisms underlying the developmental origins of health and disease [ 15 ]. We focused on the HTR2A gene in this study because it is a strong candidate for the fetal programming of future behavior and metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…The molecular mechanisms underlying these associations are not yet clearly understood. However, they may involve epigenetic changes in the fetal genome that occur in response to an altered intrauterine environment [ 13 , 14 ]. DNA methylation, an epigenetic process in which methyl groups are covalently linked to cytosines, typically within CpG dinucleotides, is particularly sensitive to environmental influences during early development.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Maternal Metabolic State and Fetal Sex and Genotype Modulate Methylation of the Serotonin Receptor Type 2A Gene (HTR2A) in the Human Placenta

et al. 2022

View full text Add to dashboard Cite

The serotonin receptor 2A gene (HTR2A) is a strong candidate for the fetal programming of future behavior and metabolism. Maternal obesity and gestational diabetes mellitus (GDM) have been associated with an increased risk of metabolic and psychological problems in offspring. We tested the hypothesis that maternal metabolic status affects methylation of HTR2A in the placenta. The prospective study included 199 pairs of mothers and healthy full-term newborns. Genomic DNA was extracted from feto-placental samples and analyzed for genotypes of two polymorphisms (rs6311, rs6306) and methylation of four cytosine residues (−1665, −1439, −1421, −1224) in the HTR2A promoter region. Placental HTR2A promoter methylation was higher in male than female placentas and depended on both rs6311 and rs6306 genotypes. A higher maternal pre-gestational body mass index (pBMI) and, to a lesser extent, diagnosis of GDM were associated with reduced HTR2A promoter methylation in female but not male placentas. Higher pBMI was associated with reduced methylation both directly and indirectly through increased GDM incidence. Tobacco use during pregnancy was associated with reduced HTR2A promoter methylation in male but not female placentas. The obtained results suggest that HTR2A is a sexually dimorphic epigenetic target of intrauterine exposures. The findings may contribute to a better understanding of the early developmental origins of neurobehavioral and metabolic disorders associated with altered HTR2A function.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Maternal Metabolic State and Fetal Sex and Genotype Modulate Methylation of the Serotonin Receptor Type 2A Gene (HTR2A) in the Human Placenta

et al. 2022

View full text Add to dashboard Cite

show abstract

“…It is hypothesized that epigenetic modifications play a role in GDM pathogenesis and exhibit the same effect on exposed offspring [ 4 , 114 ]. Researchers found that GDM-exposed offspring have an increased risk of birth defects [ 115 , 116 , 117 ].…”

Section: Epigenetic Modifications In Gdmmentioning

confidence: 99%

“…DNA methylation is the addition of a methyl group from S-adenyl methionine (SAM) to the fifth carbon (C5) position of the cytosine nucleotide to form 5-methylcytosine, which is catalyzed by methyltransferase enzymes (DNMTs) with different activities. DNMT3a and DNMT3b carry out new patterns of DNA methylation during embryogenesis (de novo), and DNMT1 maintains methylation status in cells during DNA synthesis [ 114 , 120 , 121 ]. Generally, methylation is observed at cytosine sites that are followed by guanine (CpG), but rarely at non-CpG sites (CpA, CpG, or CpT) [ 120 ].…”

Section: Epigenetic Modifications In Gdmmentioning

confidence: 99%

Genomics and Epigenomics of Gestational Diabetes Mellitus: Understanding the Molecular Pathways of the Disease Pathogenesis

Samra

Jelinek

Alsafar

et al. 2022

IJMS

View full text Add to dashboard Cite

One of the most common complications during pregnancy is gestational diabetes mellitus (GDM), hyperglycemia that occurs for the first time during pregnancy. The condition is multifactorial, caused by an interaction between genetic, epigenetic, and environmental factors. However, the underlying mechanisms responsible for its pathogenesis remain elusive. Moreover, in contrast to several common metabolic disorders, molecular research in GDM is lagging. It is important to recognize that GDM is still commonly diagnosed during the second trimester of pregnancy using the oral glucose tolerance test (OGGT), at a time when both a fetal and maternal pathophysiology is already present, demonstrating the increased blood glucose levels associated with exacerbated insulin resistance. Therefore, early detection of metabolic changes and associated epigenetic and genetic factors that can lead to an improved prediction of adverse pregnancy outcomes and future cardio-metabolic pathologies in GDM women and their children is imperative. Several genomic and epigenetic approaches have been used to identify the genes, genetic variants, metabolic pathways, and epigenetic modifications involved in GDM to determine its etiology. In this article, we explore these factors as well as how their functional effects may contribute to immediate and future pathologies in women with GDM and their offspring from birth to adulthood. We also discuss how these approaches contribute to the changes in different molecular pathways that contribute to the GDM pathogenesis, with a special focus on the development of insulin resistance.

show abstract

“…Epigenomic changes in offspring induced by maternal diabetes have been the focus of multiple research projects ( Table 2 ) and are discussed in various review articles [ 22 , 55 , 56 , 57 , 58 , 59 ]. Therefore, only major findings from selected studies will be discussed here.…”

Section: (Epi)genetic Factors Affecting Offspring Outcomes After Exposure To Maternal Diabetesmentioning

confidence: 99%

Developmental Effects of (Pre-)Gestational Diabetes on Offspring: Systematic Screening Using Omics Approaches

Shashikadze¹,

Flenkenthaler²,

Stöckl³

et al. 2021

Genes

View full text Add to dashboard Cite

Worldwide, gestational diabetes affects 2–25% of pregnancies. Due to related disturbances of the maternal metabolism during the periconceptional period and pregnancy, children bear an increased risk for future diseases. It is well known that an aberrant intrauterine environment caused by elevated maternal glucose levels is related to elevated risks for increased birth weights and metabolic disorders in later life, such as obesity or type 2 diabetes. The complexity of disturbances induced by maternal diabetes, with multiple underlying mechanisms, makes early diagnosis or prevention a challenging task. Omics technologies allowing holistic quantification of several classes of molecules from biological fluids, cells, or tissues are powerful tools to systematically investigate the effects of maternal diabetes on the offspring in an unbiased manner. Differentially abundant molecules or distinct molecular profiles may serve as diagnostic biomarkers, which may also support the development of preventive and therapeutic strategies. In this review, we summarize key findings from state-of-the-art Omics studies addressing the impact of maternal diabetes on offspring health.

show abstract

Epigenetic Changes in Gestational Diabetes Mellitus

Cited by 35 publications

References 75 publications

Maternal Metabolic State and Fetal Sex and Genotype Modulate Methylation of the Serotonin Receptor Type 2A Gene (HTR2A) in the Human Placenta

Maternal Metabolic State and Fetal Sex and Genotype Modulate Methylation of the Serotonin Receptor Type 2A Gene (HTR2A) in the Human Placenta

Genomics and Epigenomics of Gestational Diabetes Mellitus: Understanding the Molecular Pathways of the Disease Pathogenesis

Developmental Effects of (Pre-)Gestational Diabetes on Offspring: Systematic Screening Using Omics Approaches

Contact Info

Product

Resources

About