Epigenetic responses and the developmental origins of health and disease

Goyal, Dipali; Limesand, Sean W.; Goyal, Ravi

doi:10.1530/joe-19-0009

Cited by 169 publications

(125 citation statements)

References 163 publications

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“…Accumulating evidence supports that adiposity may be epigenetically regulated and programmed in utero [31][32][33]. However, the biological pathways involved, as well as the influence of the various intrauterine exposures (e.g., maternal obesity and GDM) on epivariations "programming" are yet to be identified.…”

Section: Discussionmentioning

confidence: 99%

Mediation Analysis Supports a Causal Relationship between Maternal Hyperglycemia and Placental DNA Methylation Variations at the Leptin Gene Locus and Cord Blood Leptin Levels

Gagné-Ouellet

Breton

Thibeault

et al. 2020

IJMS

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Changes in fetal DNA methylation (DNAm) of the leptin (LEP) gene have been associated with exposure to maternal hyperglycemia, but their links with childhood obesity risk are still unclear. We investigated the association between maternal hyperglycemia, placental LEP DNAm (25 5′-C-phosphate-G-3′ (CpG) sites), neonatal leptinemia, and adiposity (i.e., BMI and skinfold thickness (ST) (subscapular (SS) + triceps (TR) skinfold measures, and the ratio of SS:TR) at 3-years-old, in 259 mother–child dyads, from Gen3G birth cohort. We conducted multivariate linear analyses adjusted for gestational age at birth, sex of the child, age at follow-up, and cellular heterogeneity. We assessed the causal role of DNAm in the association between maternal glycemia and childhood outcomes, using mediation analysis. We found three CpGs associated with neonatal leptinemia (p ≤ 0.002). Of these, cg05136031 and cg15758240 were also associated with BMI (β = −2.69, p = 0.05) and fat distribution (β = −0.581, p = 0.05) at 3-years-old, respectively. Maternal glycemia was associated with DNAm at cg15758240 (β = −0.01, p = 0.04) and neonatal leptinemia (β = 0.19, p = 0.004). DNAm levels at cg15758240 mediates 0.8% of the association between maternal glycemia and neonatal leptinemia (p < 0.001). Our results support that DNAm regulation of the leptin pathway in response to maternal glycemia might be involved in programming adiposity in childhood.

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Section: Discussionmentioning

confidence: 99%

Mediation Analysis Supports a Causal Relationship between Maternal Hyperglycemia and Placental DNA Methylation Variations at the Leptin Gene Locus and Cord Blood Leptin Levels

Gagné-Ouellet

Breton

Thibeault

et al. 2020

IJMS

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“…that transduce inside cells to cause DNA methylation and histone modification leading to altered gene expression (6,65). Non-coding RNAs (microRNAs) and long non-coding RNAs also regulate post-transcriptional gene expression (6,65,66). Such altered gene expression caused by epigenetic influences can occur as early as in the fetus within a pregnant diabetic but may accumulate throughout life with recurrent stressinduced influences (66,67).…”

Section: Genes Environmental Factors Epigenetic Changesmentioning

confidence: 99%

“…Non-coding RNAs (microRNAs) and long non-coding RNAs also regulate post-transcriptional gene expression (6,65,66). Such altered gene expression caused by epigenetic influences can occur as early as in the fetus within a pregnant diabetic but may accumulate throughout life with recurrent stressinduced influences (66,67). Altered gene expression as a result of epigenetic changes leads to cell hypertrophy, proliferation, remodeling, and apoptotic signaling and are key factors for the development and progression of diabetic complications (6,64,65).…”

Section: Genes Environmental Factors Epigenetic Changesmentioning

confidence: 99%

Diabetic Retinopathy–An Underdiagnosed and Undertreated Inflammatory, Neuro-Vascular Complication of Diabetes

Sinclair

Schwartz

2019

Front. Endocrinol.

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Diabetes mellitus is a world-wide epidemic and diabetic retinopathy, a devastating, vision-threatening condition, is one of the most common diabetes-specific complications. Diabetic retinopathy is now recognized to be an inflammatory, neuro-vascular complication with neuronal injury/dysfunction preceding clinical microvascular damage. Importantly, the same pathophysiologic mechanisms that damage the pancreatic β-cell (e.g., inflammation, epigenetic changes, insulin resistance, fuel excess, and abnormal metabolic environment), also lead to cell and tissue damage causing organ dysfunction, elevating the risk of all complications, including diabetic retinopathy. Viewing diabetic retinopathy within the context whereby diabetes and all its complications arise from common pathophysiologic factors allows for the consideration of a wider array of potential ocular as well as systemic treatments for this common and devastating complication. Moreover, it also raises the importance of the need for methods that will provide more timely detection and prediction of the course in order to address early damage to the neurovascular unit prior to the clinical observation of microangiopathy. Currently, treatment success is limited as it is often initiated far too late and after significant neurodegeneration has occurred. This forward-thinking approach of earlier detection and treatment with a wider array of possible therapies broadens the physician's armamentarium and increases the opportunity for prevention and early treatment of diabetic retinopathy with preservation of good vision, as well the prevention of similar destructive processes occurring among other organs.

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“…Moreover, epigenetics can provide key mechanistic evidence for the developmental origins of health and disease (DOHaD) hypothesis (Goyal et al 2019). The DOHaD concept was proposed as a means to explain epidemiological evidence linking early life exposure to environmental factors with the onset of adverse health effects later in life (Barouki et al 2018;Barrett 2017;Bianco-Miotto et al 2017).…”

Section: Epigenetics and Its Growing Role In Environmental Epidemiologymentioning

confidence: 99%

The Promises and Challenges of Toxico-Epigenomics: Environmental Chemicals and Their Impacts on the Epigenome

Chung

Herceg

2020

Environ Health Perspect

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BACKGROUND: It has been estimated that a substantial portion of chronic and noncommunicable diseases can be caused or exacerbated by exposure to environmental chemicals. Multiple lines of evidence indicate that early life exposure to environmental chemicals at relatively low concentrations could have lasting effects on individual and population health. Although the potential adverse effects of environmental chemicals are known to the scientific community, regulatory agencies, and the public, little is known about the mechanistic basis by which these chemicals can induce long-term or transgenerational effects. To address this question, epigenetic mechanisms have emerged as the potential link between genetic and environmental factors of health and disease. OBJECTIVES: We present an overview of epigenetic regulation and a summary of reported evidence of environmental toxicants as epigenetic disruptors. We also discuss the advantages and challenges of using epigenetic biomarkers as an indicator of toxicant exposure, using measures that can be taken to improve risk assessment, and our perspectives on the future role of epigenetics in toxicology. DISCUSSION: Until recently, efforts to apply epigenomic data in toxicology and risk assessment were restricted by an incomplete understanding of epigenomic variability across tissue types and populations. This is poised to change with the development of new tools and concerted efforts by researchers across disciplines that have led to a better understanding of epigenetic mechanisms and comprehensive maps of epigenomic variation. With the foundations now in place, we foresee that unprecedented advancements will take place in the field in the coming years.

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Epigenetic responses and the developmental origins of health and disease

Abstract: Maternal and paternal factors influence offspring development and program its genome for successful postnatal life.

Cited by 169 publications

References 163 publications

Mediation Analysis Supports a Causal Relationship between Maternal Hyperglycemia and Placental DNA Methylation Variations at the Leptin Gene Locus and Cord Blood Leptin Levels

Mediation Analysis Supports a Causal Relationship between Maternal Hyperglycemia and Placental DNA Methylation Variations at the Leptin Gene Locus and Cord Blood Leptin Levels

Diabetic Retinopathy–An Underdiagnosed and Undertreated Inflammatory, Neuro-Vascular Complication of Diabetes

The Promises and Challenges of Toxico-Epigenomics: Environmental Chemicals and Their Impacts on the Epigenome

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