From cutting edge to guideline: A first step in harmonization of the zebrafish embryotoxicity test (ZET) by describing the most optimal test conditions and morphology scoring system

Beekhuijzen, Manon; Koning, Coco de; Flores-Guillén, Maria-Eugenia; Vries-Buitenweg, Selinda de; Tobor-Kaplon, Marysia; Waart, Beppy van de; Emmen, Harry

doi:10.1016/j.reprotox.2015.06.050

Cited by 118 publications

(114 citation statements)

References 43 publications

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“…Compound uptake and distribution was determined within ZF during 96 hr of exposure using two methods: (1) visualization after exposure to seven dyes with a wide range of logP values (–4.63 to 9.81), and (2) measurements of internal concentrations with LC‐MS bioanalysis after exposure to three compounds with different logP values (–1.56 to 1.8; see Table for overview of compounds used). For all experiments, we applied procedures based on suggestions for harmonization of the ZET, as previously described by our group (Beekhuijzen, ): –Test chambers were presoaked in test solutions for at least 24 hr to avoid test compound concentration losses due to compound sorption to the well walls. –Preselection of eggs was performed using an Olympus CK2 ULWCD 0.3 light‐microscope. Only fertilized eggs with a round chorion and no signs of coagulation, were selected.…”

Section: Methodsmentioning

confidence: 99%

Visualizing Compound Distribution during Zebrafish Embryo Development: The Effects of Lipophilicity and DMSO

Koning¹,

Beekhuijzen²,

Tobor-Kaplon³

et al. 2015

Birth Defects Research Pt B

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The predictability of the zebrafish embryo model is highly influenced by internal exposure of the embryo/larva. As compound uptake is likely to be influenced by factors such as lipophilicity, solvent use, and chorion presence, this article focuses on investigating their effects on compound distribution within the zebrafish embryo. To visualize compound uptake and distribution, zebrafish embryos were exposed for 96 hr, starting at 4 hr postfertilization, to water-soluble dyes: Schiff's reagent (logP -4.63), Giemsa stain (logP -0.77), Van Gierson stain (logP 1.64), Cresyl fast violet (logP 3.5), Eosine Y (logP 4.8), Sudan III (logP 7.5), and Oil red O (logP 9.81), with and without 1% dimethyl-sulfoxide (DMSO). Three additional compounds were used to analytically determine the uptake and distribution: Acyclovir (logP -1.56), Zidovudine (logP 0.05), and Metoprolol Tartrate Salt (logP 1.8). Examinations were performed every 24 hr. Both methods (visualization and specific analysis) showed that exposure to higher logP values results in higher compound uptake. Specific analysis showed that for lipophilic compounds >90% of compound is taken up by the embryo. For hydrophilic compounds, >90% of compound within the complete egg could not be associated to embryo or chorion and is probably distributed into the perivitelline space. Overall, internal exposure analyses on at least two occasions (i.e., before and after hatching) is crucial for interpretation of zebrafish embryotoxicity data, especially for compounds with extreme logP values. DMSO did not affect exposure when examined with the visualization method, however, this method might be not sensitive enough to draw hard conclusions.

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Section: Methodsmentioning

confidence: 99%

Visualizing Compound Distribution during Zebrafish Embryo Development: The Effects of Lipophilicity and DMSO

Koning¹,

Beekhuijzen²,

Tobor-Kaplon³

et al. 2015

Birth Defects Research Pt B

Self Cite

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“…; Beekhuijzen et al. ). Raising healthy female and male zebrafish is also very important for obtaining healthy eggs (discussed in the “Zebrafish housing” section).…”

Section: Selection and Number Of Eggsmentioning

confidence: 99%

“…For the assessment of teratogenicity, a large number of embryos per concentration is also preferable to increase the accuracy (Beekhuijzen et al. ).…”

Section: Selection and Number Of Eggsmentioning

confidence: 99%

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Using zebrafish in systems toxicology for developmental toxicity testing

Nishimura

Inoue

Sasagawa

et al. 2016

Congenital Anomalies

170

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With the high cost and the long-term assessment of developmental toxicity testing in mammals, the vertebrate zebrafish has become a useful alternative model organism for high-throughput developmental toxicity testing. Zebrafish is also very favorable for the 3R perspective in toxicology; however, the methodologies used by research groups vary greatly, posing considerable challenges to integrative analysis. In this review, we discuss zebrafish developmental toxicity testing, focusing on the methods of chemical exposure, the assessment of morphological abnormalities, housing conditions and their effects on the production of healthy embryos, and future directions. Zebrafish as a systems toxicology model has the potential to elucidate developmental toxicity pathways, and to provide a sound basis for human health risk assessments.

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“…Although humans have a greater biological complexity than most model organisms (Figure 3), the gene regulatory networks that connect stress response and developmental pathways in humans may be conserved in model organisms, such as C. elegans, Drosophila , and zebrafish. If so, these small model organisms can provide a useful HTS platform to assess potential hazard of developmental toxicity and teratogenesis in humans (Sipes et al 2011b; Rand et al 2014; Beekhuijzen et al 2015; Boyd et al 2016). …”

Section: Developmental Pathways and Toxicity Assessmentmentioning

confidence: 99%

Applying evolutionary genetics to developmental toxicology and risk assessment

Leung

Procter

Goldstone

et al. 2017

Reproductive Toxicology

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Evolutionary thinking continues to challenge our views on health and disease. Yet, there is a communication gap between evolutionary biologists and toxicologists in recognizing the connections among developmental pathways, high-throughput screening, and birth defects in humans. To increase our capability in identifying potential developmental toxicants in humans, we propose to apply evolutionary genetics to improve the experimental design and data interpretation with various in vitro and whole-organism models. We review five molecular systems of stress response and update 18 consensual cell-cell signaling pathways that are the hallmark for early development, organogenesis, and differentiation; and revisit the principles of teratology in light of recent advances in high-throughput screening, big data techniques, and systems toxicology. Multiscale systems modeling plays an integral role in the evolutionary approach to cross-species extrapolation. Phylogenetic analysis and comparative bioinformatics are both valuable tools in identifying and validating the molecular initiating events that account for adverse developmental outcomes in humans. The discordance of susceptibility between test species and humans (ontogeny) reflects their differences in evolutionary history (phylogeny). This synthesis not only can lead to novel applications in developmental toxicity and risk assessment, but also can pave the way for applying an evo-devo perspective to the study of developmental origins of health and disease.

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From cutting edge to guideline: A first step in harmonization of the zebrafish embryotoxicity test (ZET) by describing the most optimal test conditions and morphology scoring system

Cited by 118 publications

References 43 publications

Visualizing Compound Distribution during Zebrafish Embryo Development: The Effects of Lipophilicity and DMSO

Visualizing Compound Distribution during Zebrafish Embryo Development: The Effects of Lipophilicity and DMSO

Using zebrafish in systems toxicology for developmental toxicity testing

Applying evolutionary genetics to developmental toxicology and risk assessment

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