Developmental origins of health and disease

Heindel, Jerrold J.; Vandenberg, Laura N.

doi:10.1097/mop.0000000000000191

Cited by 310 publications

(123 citation statements)

References 51 publications

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“…Several studies have already documented that hundreds of epi-genotoxic molecules, present in the placentas and umbilical cords, interfere with cell and tissue programming. This field of investigation supports the Developmental Origins of Health and Disease theory (DOHaD), based on the concept that the ‘early life environment’ has remarkable consequences for the adult health [1]. In particular, it is suggested that fetal cells might undergo reactive epigenetic changes, which represent potentially adaptive-defensive responses to environmental factors (fetal programming).…”

Section: Introductionsupporting

confidence: 57%

Environmental Carcinogenesis and Transgenerational Transmission of Carcinogenic Risk: From Genetics to Epigenetics

Burgio¹,

Piscitelli²,

Colao

2018

IJERPH

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The dominant pathogenic model, somatic mutation theory (SMT), considers carcinogenesis as a ‘genetic accident’ due to the accumulation of ‘stochastic’ DNA mutations. This model was proposed and accepted by the scientific community when cancer mainly affected the elderly, but it does not explain the epidemiological observation of the continuous increase in cancer incidence among children and young adults. Somatic mutation theory has been proposed for a revision based on the emerging experimental evidence, as it does not fully address some issues that have proven to be crucial for carcinogenesis, namely: the inflammatory context of cancer; the key role played by the stroma, microenvironment, endothelial cells, activated macrophages, and surrounding tissues; and the distorted developmental course followed by the neoplastic tissue. Furthermore, SMT is often not able to consider either the existence of specific mutations resulting in a well-defined cancer type, or a clear relationship between mutations and tumor progression. Moreover, it does not explain the mechanism of action of the non-mutagenic and environmental carcinogens. In the last decade, cancer research has highlighted the prominent role of an altered regulation of gene expression, suggesting that cancer should be considered as a result of a polyclonal epigenetic disruption of stem/progenitor cells, mediated by tumour-inducing genes. The maternal and fetal exposure to a wide range of chemicals and environmental contaminants is raising the attention of the scientific community. Indeed, the most powerful procarcinogenic mechanisms of endocrine disruptors and other pollutants is linked to their potential to interfere epigenetically with the embryo-fetal programming of tissues and organs, altering the regulation of the genes involved in the cell cycle, cell proliferation, apoptosis, and other key signaling pathways. The embryo-fetal exposure to environmental, stressful, and proinflammatory triggers (first hit), seems to act as a ‘disease primer’, making fetal cells and tissues more susceptible to the subsequent environmental exposures (second hit), triggering the carcinogenic pathways. Furthermore, even at the molecular level, in carcinogenesis, ‘epigenetics precedes genetics’ as global DNA hypomethylation, and the hypermethylation of tumor suppressor genes are common both in cancerous and in precancerous cells, and generally precede mutations. These epigenetic models may better explain the increase of cancer and chronic/degenerative diseases in the last decades and could be useful to adopt appropriate primary prevention measures, essentially based on the reduction of maternal-fetal and child exposure to several procarcinogenic agents and factors dispersed in the environment and in the food-chains, as recently suggested by the World Health Organization.

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Section: Introductionsupporting

confidence: 57%

Environmental Carcinogenesis and Transgenerational Transmission of Carcinogenic Risk: From Genetics to Epigenetics

Burgio¹,

Piscitelli²,

Colao

2018

IJERPH

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“…For example, it is well understood that hormones have very different roles during development compared to adulthood [119, 72], thus EDCs are expected to have more potent effects during critical periods of development [120, 121]. Other environmental chemicals may also have effects that are more profound when exposures occur during development (e.g.…”

Section: A Brief Overview Of the Risk Assessment Process For Edcsmentioning

confidence: 99%

Using systematic reviews for hazard and risk assessment of endocrine disrupting chemicals

Beronius

Vandenberg

2015

Rev Endocr Metab Disord

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The possibility that endocrine disrupting chemicals (EDCs) in our environment contribute to hormonally related effects and diseases observed in human and wildlife populations has caused concern among decision makers and researchers alike. EDCs challenge principles traditionally applied in chemical risk assessment and the identification and assessment of these compounds has been a much debated topic during the last decade. State of the science reports and risk assessments of potential EDCs have been criticized for not using systematic and transparent approaches in the evaluation of evidence. In the fields of medicine and health care, systematic review methodologies have been developed and used to enable objectivity and transparency in the evaluation of scientific evidence for decision making. Lately, such approaches have also been promoted for use in the environmental health sciences and risk assessment of chemicals. Systematic review approaches could provide a tool for improving the evaluation of evidence for decision making regarding EDCs, e.g. by enabling systematic and transparent use of academic research data in this process. In this review we discuss the advantages and challenges of applying systematic review methodology in the identification and assessment of EDCs.

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“…There is increasing concern regarding the life-long neurotoxic effects of developmental exposure to environmental contaminants at levels that do not result in acute toxicity (Connors et al, 2008, Grandjean and Landrigan, 2006, 2014, Heindel and Vandenberg, 2015, Lupien et al, 2009). A group of chemicals implicated in such effects are 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD, “dioxin”) and non- ortho (“dioxin-like”) polychlorinated biphenyls (PCBs), ubiquitous contaminants that are present in up to ng/g (lipid-adjusted) quantities in human cord blood and breast milk samples, suggesting fetal or in utero exposure to low levels during early development (Crinnion, 2011, Huisman et al, 1995, Park et al, 2010, Patandin et al, 1999, Schantz et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Delayed effects of developmental exposure to low levels of the aryl hydrocarbon receptor agonist 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) on adult zebrafish behavior

2016

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Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants. The most toxic PCBs are the non-ortho-substituted (“dioxin-like”) congeners that act through the aryl hydrocarbon receptor (AHR) pathway. In humans, perinatal exposure to dioxin-like PCBs is associated with neurodevelopmental toxicity in children. Yet, the full potential for later-life neurobehavioral effects that result from early-life low level exposure to dioxin-like PCBs is not well understood. The objective of this study was to determine the effects of developmental exposure to low levels of dioxin-like PCBs on early-and later-life behavioral phenotypes using zebrafish as a model system. We exposed zebrafish embryos to either vehicle (DMSO) or low concentrations of PCB126 (0.3, 0.6, 1.2 nM) for 20 hours (4–24 hours post fertilization), and then reared them to adulthood in clean water. Locomotor activity was tested at two larval stages (7 and 14 days post fertilization). Adult fish were tested for anxiety-related behavior using the novel tank and shoaling assays. Adult behavioral assays were repeated several times on the same group of fish and effects on intra-and inter-trial habituation were determined. While there was no effect of PCB126 on larval locomotor activity in response to changes in light conditions, developmental exposure to PCB126 resulted in impaired short-and long-term habituation to a novel environment in adult zebrafish. Cyp1a induction was measured as an indicator for AHR activation. Despite high induction at early stages, cyp1a expression was not induced in the brains of developmentally exposed adult fish that showed altered behavior, suggesting that AHR was not activated at this stage. Our results demonstrate the effectiveness of the zebrafish model in detecting subtle and delayed behavioral effects resulting from developmental exposure to an environmental contaminant.

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Developmental origins of health and disease

Cited by 310 publications

References 51 publications

Environmental Carcinogenesis and Transgenerational Transmission of Carcinogenic Risk: From Genetics to Epigenetics

Environmental Carcinogenesis and Transgenerational Transmission of Carcinogenic Risk: From Genetics to Epigenetics

Using systematic reviews for hazard and risk assessment of endocrine disrupting chemicals

Delayed effects of developmental exposure to low levels of the aryl hydrocarbon receptor agonist 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) on adult zebrafish behavior

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