Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework.

Autor:	Ruiter S; Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven 3720BA-1, The Netherlands., Sippel J; Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven 3720BA-1, The Netherlands., Bouwmeester MC; Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven 3720BA-1, The Netherlands., Lommelaars T; Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven 3720BA-1, The Netherlands., Beekhof P; Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven 3720BA-1, The Netherlands. piet.beekhof@rivm.nl., Hodemaekers HM; Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven 3720BA-1, The Netherlands. hennie.hodemaekers@rivm.nl., Bakker F; Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven 3720BA-1, The Netherlands. frank.bakker@rivm.nl., van den Brandhof EJ; Centre for Environmental Quality, National Institute for Public Health and the Environment (RIVM), Bilthoven 3720BA-1, The Netherlands. evert-jan.van.den.brandhof@rivm.nl., Pennings JL; Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven 3720BA-1, The Netherlands. jeroen.pennings@rivm.nl., van der Ven LT; Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven 3720BA-1, The Netherlands. leo.van.der.ven@rivm.nl.
Jazyk:	angličtina
Zdroj:	International journal of molecular sciences [Int J Mol Sci] 2016 Nov 02; Vol. 17 (11). Date of Electronic Publication: 2016 Nov 02.
DOI:	10.3390/ijms17111830
Abstrakt:	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. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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