PPTOX III: Environmental Stressors in the Developmental Origins of Disease--Evidence and Mechanisms

Schug, Thaddeus T.; Barouki, Robert; Gluckman, Peter D.; Grandjean, Philippe; Hanson, Mark A.; Heindel, Jerold J.

doi:10.1093/toxsci/kfs267

Cited by 31 publications

(27 citation statements)

References 56 publications

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“…The high prevalence of human overweight and obesity is a major health concern that is associated with increased disease susceptibility. In recent years, it has become clear that there is an interplay between exposure to environmental chemicals, and obesity and/or dietary stress (Schug et al ., ).…”

Section: Introductionmentioning

confidence: 97%

Enhanced susceptibility of obese mice to glycidamide‐induced sperm chromatin damage without increased oxidative stress

et al. 2016

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Diet-induced obesity is known to impair male reproduction and may aggravate the male reproductive toxicity of the food contaminant acrylamide. Exposure of male mice to acrylamide induces paternally mediated pre- and post-implantation losses because of spermatozoal toxicity and these effects are potentiated in mice fed a high-fat diet. Glycidamide - an acrylamide metabolite - is the primary mediator of reproductive effects in males. The mechanisms causing the interaction between diet and acrylamide are not clear. However, diet-induced obesity is associated with oxidative stress in male reproductive tissues which might contribute to increased germ cell susceptibility. In this study, we investigated whether a moderate diet-induced obesity regimen could interfere with glycidamide-induced spermatozoal toxicity and increase oxidative stress. For this purpose, sperm chromatin integrity, oxidised DNA and protein levels, transcript levels of oxidative stress responsive genes and glycidamide-induced DNA and haemoglobin adducts were analysed in samples from male mice exposed to a high-fat diet for 6 weeks in combination with a single glycidamide exposure 7 days prior to sacrifice. We found that glycidamide-induced sperm DNA fragmentation was markedly higher in obese than in lean mice. However, the levels of oxidised DNA and/or protein in blood, liver and testicular tissue was lower in obese than in lean mice. Accompanying the reduced level of oxidised macromolecules, the transcript levels of several oxidative stress-related genes were altered in the liver and testis from obese mice suggesting induction of an antioxidant response in these animals. The haemoglobin-glycidamide adduct levels were higher in obese than in lean animals, whereas obesity did not seem to increase the level of glycidamide-induced DNA adducts. These findings show that a moderate diet-induced obesity regimen may potentiate glycidamide-induced sperm cells toxicity and suggest that the increase in glycidamide-induced sperm toxicity observed in obese mice does not depend on overt oxidative stress.

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Section: Introductionmentioning

confidence: 97%

Enhanced susceptibility of obese mice to glycidamide‐induced sperm chromatin damage without increased oxidative stress

et al. 2016

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“…Developmental exposures to environmental toxicants can be highly disruptive to embryonic development, producing outcomes ranging from embryonic lethality and congenital malformations, to subtle physiological or morphological alterations that may predispose individuals to diseases that emerge later in life [1–4]. Classically, developmental studies have focused on teratogenic outcomes, with many of these effects arising from public crises such as those caused by diethylstilbestrol and thalidomide.…”

Section: Introductionmentioning

confidence: 99%

Assessment of Toxicological Perturbations and Variants of Pancreatic Islet Development in the Zebrafish Model

Sant

Jacobs

et al. 2016

Toxics

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The pancreatic islets, largely comprised of insulin-producing beta cells, play a critical role in endocrine signaling and glucose homeostasis. Because they have low levels of antioxidant defenses and a high perfusion rate, the endocrine islets may be a highly susceptible target tissue of chemical exposures. However, this endpoint, as well as the integrity of the surrounding exocrine pancreas, is often overlooked in studies of developmental toxicology. Disruption of development by toxicants can alter cell fate and migration, resulting in structural alterations that are difficult to detect in mammalian embryo systems, but that are easily observed in the zebrafish embryo model (Danio rerio). Using endogenously expressed fluorescent protein markers for developing zebrafish beta cells and exocrine pancreas tissue, we documented differences in islet area and incidence rates of islet morphological variants in zebrafish embryos between 48 and 96 h post fertilization (hpf), raised under control conditions commonly used in embryotoxicity assays. We identified critical windows for chemical exposures during which increased incidences of endocrine pancreas abnormalities were observed following exposure to cyclopamine (2–12 hpf), Mono-2-ethylhexyl phthalate (MEHP) (3–48 hpf), and Perfluorooctanesulfonic acid (PFOS) (3–48 hpf). Both islet area and length of the exocrine pancreas were sensitive to oxidative stress from exposure to the oxidant tert-butyl hydroperoxide during a highly proliferative critical window (72 hpf). Finally, pancreatic dysmorphogenesis following developmental exposures is discussed with respect to human disease.

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“…Examples of association between exposure to environmental stressors during critical periods of fetal development and increased risk for cardiovascular diseases, obesity and neurological disorders are well documented [3,4]. This is a growing field of research and is collectively termed as the developmental origins of health and disease (DOHaD) [5,6].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic effects of environmental chemicals: Insights from zebrafish

Aluru

2017

Current Opinion in Toxicology

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Zebrafish have been extensively used for studying vertebrate development and modeling human diseases such as cancer. In the last two decades, they have also emerged as an important model for developmental toxicology research and, more recently, for studying the developmental origins of health and disease (DOHaD). It is widely recognized that epigenetic mechanisms mediate the persistent effects of exposure to chemicals during sensitive windows of development. There is considerable interest in understanding the epigenetic mechanisms associated with DOHaD using zebrafish as a model system. This review summarizes our current knowledge on the effects of environmental chemicals on DNA methylation, histone modifications and noncoding RNAs in the context of DOHaD, and suggest some key considerations in designing experiments for characterizating the mechanisms of action.

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PPTOX III: Environmental Stressors in the Developmental Origins of Disease--Evidence and Mechanisms

Cited by 31 publications

References 56 publications

Enhanced susceptibility of obese mice to glycidamide‐induced sperm chromatin damage without increased oxidative stress

Enhanced susceptibility of obese mice to glycidamide‐induced sperm chromatin damage without increased oxidative stress

Assessment of Toxicological Perturbations and Variants of Pancreatic Islet Development in the Zebrafish Model

Epigenetic effects of environmental chemicals: Insights from zebrafish

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