Exposure to Gestational Diabetes Mellitus (GDM) alters DNA methylation in placenta and fetal cord blood

Awamleh, Zain; Butcher, Darci T.; Hanley, Anthony J.; Retnakaran, Ravi; Haertle, Larissa; Haaf, Thomas; Hamilton, Jill; Weksberg, Rosanna

doi:10.1016/j.diabres.2021.108690

Cited by 26 publications

(32 citation statements)

References 43 publications

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“…Known as a highly specialized organ during pregnancy, the placenta serves as the interface between maternal and fetal circulation (35). In recent years, the key role of the placenta in the occurrence and development of GDM has been reported by multiple studies (36)(37)(38). Currently, IR is the critical pathophysiological characteristic of GDM, which is also found during normal pregnancy.…”

Section: Discussionmentioning

confidence: 99%

NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency

Tan

et al. 2021

Exp Ther Med

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The placenta may play a key role in the activation of inflammation and initiation of insulin resistance (IR) during gestational diabetes mellitus (GDM) pathogenesis. Interleukin (IL)-1β and IL-18, regulated by NLR family pyrin domain containing-3 (NLRP3) inflammasome, are important inflammatory cytokines in the initiation of maternal IR during GDM. However, the mechanism responsible for the regulatory of NLRP3 inflammasome in placenta remains unknown. Hydrogen sulfide (H 2 S) exerts anti-inflammatory function partially via suppressing the activation of the NLPR3 inflammasome. The present study aimed to investigate the role of NLRP3 inflammasome, H 2 S synthetase cystathionine-γ-lyase (CSE) and cystathionine-β-synthetase (CBS) in placenta in the pathogenesis of GDM. Clinical placenta samples were collected from pregnant women with GDM (n=16) and healthy pregnant women at term (n=16). Western blot analysis was performed to detect the protein expression levels of NLRP3, cleaved caspase-1, CBS and CSE in the placenta samples. Pearson's correlation analysis was performed to assess the correlation between NLRP3 inflammasome and H 2 S synthetase. Human placental cells were cultured and treated with different concentrations of NaHS (0, 10, 25 and 50 nmol/l) or L-cysteine (0, 0.25, 0.50 and 1.00 mmol/l). In addition, western blot analysis was performed to detect the protein expression levels of NLRP3 and cleaved caspase-1, while ELISA was performed to measure the production of IL-1β and IL-18 in the culture media. The results demonstrated that the expression levels of NLRP3 and cleaved caspase-1 increased, while the expression levels of CBS and CSE decreased in the placenta samples. In addition, the expression levels of NLRP3 and cleaved caspase-1 were inversely correlated with the expression levels of CBS and CSE. Notably, NaHS and L-cysteine significantly suppressed the expression levels of NLRP3 and cleaved caspase-1, and the production of IL-1 and IL-18 in human placental cells. Taken together, the results of the present study suggest that H 2 S synthetase deficiency in placenta may contribute to excessive activation of NLRP3 inflammasome in GDM.

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Section: Discussionmentioning

confidence: 99%

NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency

Tan

et al. 2021

Exp Ther Med

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“…Several studies confirmed a different DNA methylation pattern in GDM pregnancies when compared to healthy pregnant women. The DNA methylation in 42 fetal cord blood and 36 placenta samples was analyzed in a study by Awamleh et al [ 75 ]. They identified 662 and 99 CpG sites in GDM placenta and cord blood, respectively.…”

Section: Epigenetics In Gdmmentioning

confidence: 99%

Epigenetic Changes in Gestational Diabetes Mellitus

Dłuski

Wolińska

Skrzypczak

2021

IJMS

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Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance that appears or is for the first time diagnosed during pregnancy. It can lead to many complications in the mother and in the offspring, so diagnostics and management of GDM are important to avoid adverse pregnancy outcomes. Epigenetic studies revealed the different methylation status of genes in pregnancies with GDM compared to pregnancies without GDM. A growing body of evidence shows that the GDM can affect not only the course of the pregnancy, but also the development of the offspring, thus contributing to long-term effects and adverse health outcomes of the progeny. Epigenetic changes occur through histone modification, DNA methylation, and disrupted function of non-coding ribonucleic acid (ncRNA) including microRNAs (miRNAs). In this review, we focus on the recent knowledge about epigenetic changes in GDM. The analysis of this topic may help us to understand pathophysiological mechanisms in GDM and find a solution to prevent their consequences.

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“…Epigenetic modifications associated with GDM are thought to influence the susceptibility to metabolic disorders in offspring. [4][5][6][7][8][9][10][11][12] An overview of genome-wide methylation analyses of GDM using cord blood obtained from earlier empirical studies is shown in table 3. In all studies, epigenetic changes were detected in metabolic mechanisms-related genes; however, in those reports, the maternal glycemic state during pregnancy and fetal information were not described in detail, and the studies included small cohorts.…”

Section: Discussionmentioning

confidence: 99%

“…Pathophysiology/complications genes. [4][5][6][7][8][9][10][11][12] Based on these studies, the mechanisms of future metabolic syndrome and obesity development were evaluated from an epigenetic perspective. However, these studies were based on small cohorts and did not characterize the maternal glycemic status during pregnancy nor provided detailed fetal/neonatal information.…”

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confidence: 99%

DNA methylation analysis of cord blood samples in neonates born to gestational diabetes mothers diagnosed before 24 gestational weeks

Kasuga

Kawai

Miyakoshi

et al. 2022

BMJ Open Diab Res Care

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IntroductionGenome-wide methylation analyses of gestational diabetes mellitus (GDM) diagnosed after 24 gestational weeks (late GDM (L-GDM)) using cord blood have been reported. However, epigenetic changes in neonates born to mothers with GDM diagnosed before 24 gestational weeks (early GDM (E-GDM)) have not been reported. We investigated DNA methylation in neonates born to mothers with E-GDM using cord blood samples.Research design and methodsGenome-wide DNA methylation analysis was performed using an Illumina EPIC array to compare methylation rates of 754 255 autosomal sites in cord blood samples from term neonates born to 162 mothers with GDM (E-GDM: n=84, L-GDM: n=78) and 60 normal glucose tolerance (normal OGTT) pregnancies. GDM was diagnosed based on Japan Society of Obstetrics and Gynecology criteria modified with International Association of Diabetes in Pregnancy Study Group criteria. In this study, all GDM mothers underwent dietary management, while self-monitoring of blood glucose and insulin administration was initiated when dietary modification did not achieve glycemic control.ResultsThere were no significant differences in genome-wide DNA methylation of cord blood samples between the GDM (E-GDM and L-GDM) groups and normal OGTT group or between the E-GDM and normal OGTT groups, L-GDM and normal OGTT groups, and E-GDM and L-GDM groups.ConclusionsThis is the first report to determine the DNA methylation patterns in neonates born to mothers with E-GDM. Neonates born to mothers with GDM, who were diagnosed based on Japan Society of Obstetrics and Gynecology criteria, may not differ in DNA methylation compared with those born to normal OGTT mothers.

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Exposure to Gestational Diabetes Mellitus (GDM) alters DNA methylation in placenta and fetal cord blood

Cited by 26 publications

References 43 publications

NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency

NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency

Epigenetic Changes in Gestational Diabetes Mellitus

DNA methylation analysis of cord blood samples in neonates born to gestational diabetes mothers diagnosed before 24 gestational weeks

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