Molecular mechanisms underlying the fetal programming of adult disease

Vo, Thin Xuan; Hardy, Daniel B.

doi:10.1007/s12079-012-0165-3

Cited by 46 publications

(30 citation statements)

References 172 publications

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“…Physiological epigenetic processes act in cell-specific and temporally regulated manners to influence normal development, tissue formation, differentiation, and aging 10, 12, 13 . Epigenetics also plays a critical role in the fetal programming of adult disease 3, 69, 73, 74 .…”

Section: Influences Of Epigenetics On Embryonic Developmentmentioning

confidence: 99%

Long-term consequences of disrupting adenosine signaling during embryonic development

Rivkees

Wendler

2017

Molecular Aspects of Medicine

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There is growing evidence that disruption in the prenatal environment can have long-lasting effects on an individual’s health in adulthood. Research on the fetal programming of adult diseases, including cardiovascular disease, focuses on epi-mutations, which alter the normal pattern of epigenetic factors such as DNA methylation, miRNA expression, or chromatin modification, rather than traditional genetic alteration. Thus, understanding how in utero chemical exposures alter epigenetics and lead to adult disease is of considerable public health concern. Few signaling molecules have the potential to influence the developing mammal as the nucleoside adenosine. Adenosine levels increase rapidly with tissue hypoxia and inflammation. Adenosine antagonists including the methlyxanthines caffeine and theophylline are widely consumed during pregnancy. The receptors that transduce adenosine action are the A1, A2a, A2b, and A3 adenosine receptors (ARs). We examined the long-term effects of in utero disruption of adenosine signaling on cardiac gene expression, morphology, and function in adult offspring. One substance that fetuses are frequently exposed to is caffeine, which is a non-selective adenosine receptor antagonist. Over the past several years, we examined the role of adenosine signaling during embryogenesis and cardiac development. We discovered that in utero alteration in adenosine action leads to adverse effects on embryonic and adult murine hearts. We find that cardiac A1ARs protect the embryo from in utero hypoxic stress, a condition that causes an increase in adenosine levels. After birth in mice, we observed that in utero caffeine exposure leads to abnormal cardiac function and morphology in adults, including an impaired response to β-adrenergic stimulation. Recently, we observed that in utero caffeine exposure induces transgenerational effects on cardiac morphology, function, and gene expression. Our findings indicate that the effects of altered adenosine signaling are dependent on signaling through the A1ARs and timing of disruption. In addition, the long-term effects of altered adenosine signaling appear to be mediated by alterations in DNA methylation, an epigenetic process critical for normal development.

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Section: Influences Of Epigenetics On Embryonic Developmentmentioning

confidence: 99%

Long-term consequences of disrupting adenosine signaling during embryonic development

Rivkees

Wendler

2017

Molecular Aspects of Medicine

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“…‘perinatal programming’) within adipocytes . Recent studies suggest that the programming response involves epigenetic and transcriptional changes, endoplasmic reticulum stress and/or reactive oxygen species .…”

Section: Characteristics Of the Participantsmentioning

confidence: 99%

Longitudinal changes in infant body composition: association with childhood obesity

et al. 2014

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Summary Background Rapid weight gain in infancy has been established as a risk factor for the development of later obesity. Objective We aimed to investigate the role of changes in infant body composition (assessed via total body electrical conductivity) on the development of overweight/obesity in mid-childhood. Methods Fifty-three term infants were evaluated at birth, three times during infancy and in mid-childhood. Logistic regression was used to determine associations between rates of total weight gain, fat mass gain and lean mass gain during infancy and later overweight/obesity (defined as body mass index [BMI] ≥85th percentile), adjusted for birth weight and parent education. Results At follow-up (age 9.0 ± 1.8 years), 30% were overweight/obese. More rapid total weight gain from 0 to 4 months was associated with twofold odds (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.05–3.74, P = 0.04) of overweight/obesity in mid-childhood. From 0 to 8 months, more rapid weight gain was associated with nearly fivefold odds (OR 4.76, 95% CI 1.05–21.5, P = 0.04), and more rapid fat mass gain was associated with eightfold odds (OR 8.03, 95% CI 1.11–58.2, P = 0.04) of later overweight/obesity. Conclusion This exploratory study suggests that rapid weight gain, especially fat mass gain, in earlier infancy predisposes to mid-childhood overweight/obesity.

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“…Epigenetic alterations indicate modifications in DNA without changes in DNA sequence through DNA methylation, post-translational histone modifications, modification of nuclear receptors, and microRNAs. 32,33 Clinical studies that examine epigenetic modification and clinical outcomes in childhood are limited. An example of a recent study that applied epigenetic strategies to cardiovascular pathophysiology in the young was reported by Breton et al 34 These investigators measured DNA methylation of nitric oxide synthase (NOS) and identified an association of percent DNA methylation of NOS1 with carotid inima-media thickness in children.…”

Section: Birth Weight and Intrauterine Effects On Childhood Bpmentioning

confidence: 99%

Recent Clinical and Translational Advances in Pediatric Hypertension

Falkner

2015

Hypertension

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Molecular mechanisms underlying the fetal programming of adult disease

Cited by 46 publications

References 172 publications

Long-term consequences of disrupting adenosine signaling during embryonic development

Long-term consequences of disrupting adenosine signaling during embryonic development

Longitudinal changes in infant body composition: association with childhood obesity

Recent Clinical and Translational Advances in Pediatric Hypertension

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