Combining mouse embryonic stem cells and zebrafish embryos to evaluate developmental toxicity of chemical exposure

Javier Conde-Vancells; Mercedes Vazquez-Chantada; Catherine W. McCollum; Maria Bondesson; Sharanya Maanasi Kalasekar; Bogdan J. Wlodarczyk; Jan-Ake Gustafsson; Robert M. Cabrera; Richard H. Finnell

doi:10.1016/j.reprotox.2018.07.080

Combining mouse embryonic stem cells and zebrafish embryos to evaluate developmental toxicity of chemical exposure

Javier Conde-Vancells, Mercedes Vazquez-Chantada, Catherine W. McCollum, Maria Bondesson, Sharanya Maanasi Kalasekar, Bogdan J. Wlodarczyk, Jan-Ake Gustafsson, Robert M. Cabrera, Richard H. Finnell

Houston Methodist

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

The assays in this study utilize mouse embryonic stem cells (mESCs) and zebrafish embryos to evaluate the potential developmental toxicity of industrial and pharmaceutical chemicals. A set of eleven chemicals of known mammalian in vivo teratogenicity were tested in the assays and correlations to mammalian data. Using mESCs, proliferation, differentiation, and cytotoxicity of the chemicals were measured. In zebrafish embryos, lethality and the lowest effect level concentrations for morphological malformations were determined. Clustering of the assays based on frequency of affected assays resulted in a ranking of the test compounds that correlated to in vivo rodent data (R = 0.88, P < 0.001). We conclude that the combination of ESC- and zebrafish-based assays provides a valuable platform for the prioritization of pharmaceutical and industrial chemicals for further testing of developmental toxicity in rodents.

Original language	English (US)
Pages (from-to)	220-228
Number of pages	9
Journal	Reproductive Toxicology
Volume	81
DOIs	https://doi.org/10.1016/j.reprotox.2018.07.080
State	Published - Oct 2018

Keywords

Animal testing
Developmental toxicity
Embryonic stem cells
In vitro assay
In vivo toxicity testing
Teratogenesis
Zebrafish

ASJC Scopus subject areas

Toxicology

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10.1016/j.reprotox.2018.07.080

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Conde-Vancells, J., Vazquez-Chantada, M., McCollum, C. W., Bondesson, M., Kalasekar, S. M., Wlodarczyk, B. J., Gustafsson, J.-A., Cabrera, R. M., & Finnell, R. H. (2018). Combining mouse embryonic stem cells and zebrafish embryos to evaluate developmental toxicity of chemical exposure. Reproductive Toxicology, 81, 220-228. https://doi.org/10.1016/j.reprotox.2018.07.080

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title = "Combining mouse embryonic stem cells and zebrafish embryos to evaluate developmental toxicity of chemical exposure",

abstract = "The assays in this study utilize mouse embryonic stem cells (mESCs) and zebrafish embryos to evaluate the potential developmental toxicity of industrial and pharmaceutical chemicals. A set of eleven chemicals of known mammalian in vivo teratogenicity were tested in the assays and correlations to mammalian data. Using mESCs, proliferation, differentiation, and cytotoxicity of the chemicals were measured. In zebrafish embryos, lethality and the lowest effect level concentrations for morphological malformations were determined. Clustering of the assays based on frequency of affected assays resulted in a ranking of the test compounds that correlated to in vivo rodent data (R = 0.88, P < 0.001). We conclude that the combination of ESC- and zebrafish-based assays provides a valuable platform for the prioritization of pharmaceutical and industrial chemicals for further testing of developmental toxicity in rodents.",

keywords = "Animal testing, Developmental toxicity, Embryonic stem cells, In vitro assay, In vivo toxicity testing, Teratogenesis, Zebrafish",

author = "Javier Conde-Vancells and Mercedes Vazquez-Chantada and McCollum, {Catherine W.} and Maria Bondesson and Kalasekar, {Sharanya Maanasi} and Wlodarczyk, {Bogdan J.} and Jan-Ake Gustafsson and Cabrera, {Robert M.} and Finnell, {Richard H.}",

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year = "2018",

month = oct,

doi = "10.1016/j.reprotox.2018.07.080",

language = "English (US)",

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AU - Conde-Vancells, Javier

AU - Vazquez-Chantada, Mercedes

AU - McCollum, Catherine W.

AU - Bondesson, Maria

AU - Kalasekar, Sharanya Maanasi

AU - Wlodarczyk, Bogdan J.

AU - Gustafsson, Jan-Ake

AU - Cabrera, Robert M.

AU - Finnell, Richard H.

PY - 2018/10

Y1 - 2018/10

N2 - The assays in this study utilize mouse embryonic stem cells (mESCs) and zebrafish embryos to evaluate the potential developmental toxicity of industrial and pharmaceutical chemicals. A set of eleven chemicals of known mammalian in vivo teratogenicity were tested in the assays and correlations to mammalian data. Using mESCs, proliferation, differentiation, and cytotoxicity of the chemicals were measured. In zebrafish embryos, lethality and the lowest effect level concentrations for morphological malformations were determined. Clustering of the assays based on frequency of affected assays resulted in a ranking of the test compounds that correlated to in vivo rodent data (R = 0.88, P < 0.001). We conclude that the combination of ESC- and zebrafish-based assays provides a valuable platform for the prioritization of pharmaceutical and industrial chemicals for further testing of developmental toxicity in rodents.

AB - The assays in this study utilize mouse embryonic stem cells (mESCs) and zebrafish embryos to evaluate the potential developmental toxicity of industrial and pharmaceutical chemicals. A set of eleven chemicals of known mammalian in vivo teratogenicity were tested in the assays and correlations to mammalian data. Using mESCs, proliferation, differentiation, and cytotoxicity of the chemicals were measured. In zebrafish embryos, lethality and the lowest effect level concentrations for morphological malformations were determined. Clustering of the assays based on frequency of affected assays resulted in a ranking of the test compounds that correlated to in vivo rodent data (R = 0.88, P < 0.001). We conclude that the combination of ESC- and zebrafish-based assays provides a valuable platform for the prioritization of pharmaceutical and industrial chemicals for further testing of developmental toxicity in rodents.

KW - Animal testing

KW - Developmental toxicity

KW - Embryonic stem cells

KW - In vitro assay

KW - In vivo toxicity testing

KW - Teratogenesis

KW - Zebrafish

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Combining mouse embryonic stem cells and zebrafish embryos to evaluate developmental toxicity of chemical exposure

Abstract

Keywords

ASJC Scopus subject areas

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