Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases

Ruchat, Stéphanie-May; Houde, Andrée-Anne; Voisin, Grégory; St‐Pierre, Julie; Perron, Patrice; Baillargeon, Jean-Patrice; Gaudet, Daniel; Hivert, Marie‐France; Brisson, Diane; Bouchard, Luigi

doi:10.4161/epi.25578

Cited by 216 publications

(125 citation statements)

References 40 publications

(42 reference statements)

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“…6,7 Data from animal studies also confirmed that in vitro embryo culture is associated with changes in DNA methylation. 6,8 Further, the fact that other conditions, e.g., intrauterine growth restriction (IUGR), which have an increased incidence in ART pregnancies, have been shown to demonstrate epigenetic alterations, [9][10][11] supports the hypothesis that epigenetic deregulation at non-imprinted CpG sites may also explain some of the medical issues associated with ART.…”

Section: Introductionmentioning

confidence: 77%

Comparison of genome-wide and gene-specific DNA methylation between ART and naturally conceived pregnancies

et al. 2015

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Data linking assisted reproductive technologies (ART) with aberrant DNA methylation is limited and inconclusive. In addition, most studies to date have analyzed only a small number of CpG sites and focused on methylation changes in placentas, while data on cord blood are scarce. Our aim was to compare DNA methylation in cord blood samples from ART (N D 10) and control pregnancies (N D 8) using a genome-wide approach with the Illumina Ò Infinium Human Methylation27 array, which interrogates 27,578 CpG sites. A total of 733 (2.7%) of the CpG sites were significantly differentially methylated between the 2 groups (P < 0.05), with an overall relative hypomethylation in the ART group (P < 0.001). Differences in DNA methylation were more pronounced for CpG sites in certain types of genomic locations and were related to baseline methylation levels and distance from CpG islands and transcription start sites. ART was associated with significantly higher variation in DNA methylation, suggesting that differences in DNA methylation between cases and controls may result from stochastic (or random) genome-wide changes in DNA methylation in ART pregnancies. We identified 24 candidate genes with 2 or more CpG sites that were significantly different between the IVF and control groups. The current study provides support for the hypothesis that ART or associated subfertility may be associated with genome-wide changes in DNA methylation, and these changes appear to be, at least in part, due to epigenetic instability in ART pregnancies. Further studies are required in order to determine the extent to which such ART-related epigenetic instability may have phenotypic consequences.

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Section: Introductionmentioning

confidence: 77%

Comparison of genome-wide and gene-specific DNA methylation between ART and naturally conceived pregnancies

et al. 2015

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“…8,9 Among other studies, we have reported associations between maternal blood glucose concentrations at 2 nd trimester of pregnancy and fetal placental DNAm levels at the proximal promoter and intronic CpG island loci in the lipoprotein lipase (LPL) gene. 9 Considering that GDM had been repeatedly associated with a long-term increase in obesity risk and diabetes in offspring, our results have suggested that maternal hyperglycemia, through epigenetic modifications at LPL gene loci, could contribute to the fetal metabolic programming of chronic metabolic disorders.…”

Section: Introductionmentioning

confidence: 99%

“…8,9 However, it is essential to understand how LPL epigenetic perturbations could translate into later life changes in lipid metabolism, fat accretion, and growth.…”

Section: Introductionmentioning

confidence: 99%

Placental lipoprotein lipase DNA methylation alterations are associated with gestational diabetes and body composition at 5 years of age

et al. 2017

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Gestational diabetes mellitus (GDM) is associated with obesity in childhood. This suggests that consequences of in utero exposure to maternal hyperglycemia extend beyond the fetal development, possibly through epigenetic programming. The aims of this study were to assess whether placental DNA methylation (DNAm) marks were associated with maternal GDM status and to offspring body composition at 5 years old in a prospective birth cohort. DNAm levels were measured in the fetal side of the placenta in 66 samples (24 from GDM mothers) using bisDNA-pyrosequencing. Anthropometric and body composition (bioimpedance) were measured in children at 5 years of age. Mann-Whitney and Spearman tests were used to assess associations between GDM, placental DNAm levels at the lipoprotein lipase (LPL) locus and children's weight, height, body mass index (BMI), body fat, and lean masses at 5 years of age. Weight, height, and BMI z-scores were computed according to the World Health Organization growth chart. Analyses were adjusted for gestational age at birth, child sex, maternal age, and pre-pregnancy BMI. LPL DNAm levels were positively correlated with birth weight z-scores (r D 0.252, P D 0.04), and with midchildhood weight z-scores (r D 0.314, P D 0.01) and fat mass (r D 0.275, P D 0.04), and negatively correlated with lean mass (r D ¡0.306, P D 0.02). We found a negative correlation between LPL DNAm and mRNA levels in placenta (r D ¡0.459; P < 0.001), which highlights the regulation of transcriptional activity by these epivariations. We demonstrated that alterations in fetal placental DNAm levels at the LPL gene locus are associated with the anthropometric profile in children at 5 years of age. These findings support the concept of fetal metabolic programming through epigenetic changes.

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“…In the Canadian cohort, DNA methylation was also measured at 485,000 CpG sites, using the Infinium HumanMethylation450 BeadChips platform (Ruchat et al, 2013b). CpGs in 3271 genes were found to be affected by maternal GDM.…”

Section: Reviewmentioning

confidence: 99%

“…Significantly, MEST gene DNA methylation was downregulated by 7 percentage points in GDM (N=80 GDM patients and 83 insulin-dependent GDM patients and N=57 controls). The authors also observed a significant decrease in blood MEST methylation (3 percentage points, N=37 obese patients and 37 controls) in adults with morbid obesity, supporting the idea that intrauterine exposure to GDM may have effects on the epigenome of the offspring throughout life.In the Canadian cohort, DNA methylation was also measured at 485,000 CpG sites, using the Infinium HumanMethylation450 BeadChips platform (Ruchat et al, 2013b). CpGs in 3271 genes were found to be affected by maternal GDM.…”

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confidence: 99%

Placental contribution to nutritional programming of health and diseases: epigenetics and sexual dimorphism

Tarrade

Panchenko

Junien

et al. 2015

Journal of Experimental Biology

204

149

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The recent and rapid worldwide increase in non-communicable diseases challenges the assumption that genetic factors are the primary contributors to such diseases. A new concept of the 'developmental origins of health and disease' (DOHaD) is at stake and therefore requires a paradigm shift. Maternal obesity and malnutrition predispose offspring to develop metabolic syndrome, a vicious cycle leading to transmission to subsequent generation(s), with differences in response and susceptibility according to the sex of the individual. The placenta is a programming agent of adult health and disease. Adaptations of placental phenotype in response to maternal diet and metabolic status alter fetal nutrient supply. This implies important epigenetic changes that are, however, still poorly documented in DOHaD studies, particularly concerning overnutrition. The aim of this review is to discuss the emerging knowledge on the relationships between the effect of maternal nutrition or metabolic status on placental function and the risk of diseases later in life, with a specific focus on epigenetic mechanisms and sexual dimorphism. Explaining the sex-specific causal variables and how males versus females respond and adapt to environmental perturbations should help physicians and patients to anticipate disease susceptibility.KEY WORDS: DOHaD, Fetal programming, Placenta, Sex, Nutrition, Obesity, Maternal environment, Gestation Introduction: developmental origins of health and diseaseThe recent and rapid worldwide increase in non-communicable diseases (NCDs) challenges the assumption that genetic factors are the primary contributors to such diseases (McAllister et al., 2009). The 'developmental origins of health and disease' (DOHaD) paradigm states that the environment during the periconception, gestation and lactation periods shapes the developing individuals, leading, in the case of a deleterious environment, to a predisposition to adult-onset diseases. This theory was popularised by D. J. Barker in the early 1990s (Barker, 1990) but the question had already been raised in earlier studies. In the 1960s and 1970s, different experiments on diverse mammalian species (rat, mouse, guinea pig, pig, etc.) showed that a reduction of maternal calorie or protein intake during pregnancy and lactation affects the growth capacity and cognitive ability of the offspring (reviewed in Roeder and Chow, 1972;McCance, 1976). Later, this concept was extended to phenotype in general, with a strong implication for quantitative traits in agriculture. An increasing number of studies pointed to the fact that maternal environment in cattle was an important parameter to fully express the genetically highly selected potential of the animals (Wallace et al., 2010; Jammes et al., 2011;Tanghe et al., 2014).Male and female susceptibility to NCDs is well described. It appears that in the DOHaD context, the same environmental exposure may affect the long-term health of the offspring with a discrepancy between males and females in terms of the timing, onset ...

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Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases

Abstract: (2013) Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases, Epigenetics, 8:9,[935][936][937][938][939][940][941][942][943]

Cited by 216 publications

References 40 publications

Comparison of genome-wide and gene-specific DNA methylation between ART and naturally conceived pregnancies

Comparison of genome-wide and gene-specific DNA methylation between ART and naturally conceived pregnancies

Placental lipoprotein lipase DNA methylation alterations are associated with gestational diabetes and body composition at 5 years of age

Placental contribution to nutritional programming of health and diseases: epigenetics and sexual dimorphism

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