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-Åke 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

Reprod Toxicol. 2018 Oct:81:220-228. doi: 10.1016/j.reprotox.2018.07.080. Epub 2018 Aug 10.

Authors

Javier Conde-Vancells¹, Mercedes Vazquez-Chantada¹, Catherine W McCollum², Maria Bondesson³, Sharanya Maanasi Kalasekar², Bogdan J Wlodarczyk⁴, Jan-Åke Gustafsson², Robert M Cabrera⁴, Richard H Finnell⁵

Affiliations

¹ Dell Pediatric Research Institute, Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX 78723, United States.
² Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, United States.
³ Department of Intelligent Systems Engineering, Indiana University, Bloomington, IN 47408, United States.
⁴ Dell Pediatric Research Institute, Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX 78723, United States; Departments of Molecular and Cellular Biology and Medicine, Baylor College of Medicine, Houston, TX 77030, United States.
⁵ Dell Pediatric Research Institute, Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX 78723, United States; Departments of Molecular and Cellular Biology and Medicine, Baylor College of Medicine, Houston, TX 77030, United States. Electronic address: rfinnell@austin.utexas.edu.

PMID: 30103011
DOI: 10.1016/j.reprotox.2018.07.080

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Cell Proliferation / drug effects
Cell Survival / drug effects
Embryo, Nonmammalian / abnormalities
Embryo, Nonmammalian / drug effects*
Mice
Mouse Embryonic Stem Cells / drug effects*
Teratogens / toxicity*
Toxicity Tests / methods*
Zebrafish / abnormalities*

Substances

Teratogens