PUBLICATION
Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework
- Authors
- Ruiter, S., Sippel, J., Bouwmeester, M.C., Lommelaars, T., Beekhof, P., Hodemaekers, H.M., Bakker, F., van den Brandhof, E.J., Pennings, J.L., van der Ven, L.T.
- ID
- ZDB-PUB-161110-5
- Date
- 2016
- Source
- International Journal of Molecular Sciences 17(11): (Journal)
- Registered Authors
- van der Ven, Leo
- Keywords
- DNA methylation, S-adenosyl-methionine, adverse outcome pathway (AOP), cadmium, developmental origins of health and disease (DOHaD), epigenetics, glutathione, oxidative stress, programming, zebrafish
- MeSH Terms
-
- Adenosine/analogs & derivatives
- Adenosine/antagonists & inhibitors
- Adenosine/metabolism
- Animals
- Cadmium/toxicity*
- Cations, Divalent
- DNA Methylation/drug effects
- Dose-Response Relationship, Drug
- Embryo, Nonmammalian
- Embryonic Development/drug effects*
- Embryonic Development/genetics
- Environmental Exposure/adverse effects*
- Epigenesis, Genetic/drug effects
- Ethionine/analogs & derivatives
- Ethionine/antagonists & inhibitors
- Ethionine/metabolism
- Exploratory Behavior/drug effects*
- Gene Expression Regulation, Developmental/drug effects
- Glutathione/antagonists & inhibitors
- Glutathione/metabolism
- Oxidative Stress
- Phenotype
- Water Pollutants, Chemical/toxicity*
- Zebrafish/embryology
- Zebrafish/genetics*
- PubMed
- 27827847 Full text @ Int. J. Mol. Sci.
Citation
Ruiter, S., Sippel, J., Bouwmeester, M.C., Lommelaars, T., Beekhof, P., Hodemaekers, H.M., Bakker, F., van den Brandhof, E.J., Pennings, J.L., van der Ven, L.T. (2016) Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework. International Journal of Molecular Sciences. 17(11).
Abstract
Non-communicable diseases (NCDs) are a major cause of premature mortality. Recent studies show that predispositions for NCDs may arise from early-life exposure to low concentrations of environmental contaminants. This developmental origins of health and disease (DOHaD) paradigm suggests that programming of an embryo can be disrupted, changing the homeostatic set point of biological functions. Epigenetic alterations are a possible underlying mechanism. Here, we investigated the DOHaD paradigm by exposing zebrafish to subtoxic concentrations of the ubiquitous contaminant cadmium during embryogenesis, followed by growth under normal conditions. Prolonged behavioral responses to physical stress and altered antioxidative physiology were observed approximately ten weeks after termination of embryonal exposure, at concentrations that were 50-3200-fold below the direct embryotoxic concentration, and interpreted as altered developmental programming. Literature was explored for possible mechanistic pathways that link embryonic subtoxic cadmium to the observed apical phenotypes, more specifically, the probability of molecular mechanisms induced by cadmium exposure leading to altered DNA methylation and subsequently to the observed apical phenotypes. This was done using the adverse outcome pathway model framework, and assessing key event relationship plausibility by tailored Bradford-Hill analysis. Thus, cadmium interaction with thiols appeared to be the major contributor to late-life effects. Cadmium-thiol interactions may lead to depletion of the methyl donor S-adenosyl-methionine, resulting in methylome alterations, and may, additionally, result in oxidative stress, which may lead to DNA oxidation, and subsequently altered DNA methyltransferase activity. In this way, DNA methylation may be affected at a critical developmental stage, causing the observed apical phenotypes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping