Assessment of developmental delay in the zebrafish embryo teratogenicity assay.
In this study we analyzed some aspects of the assessment of developmental delay in the zebrafish embryotoxicity/teratogenicity test and explored the suitability of acetylcholinesterase (AChE) activity as a biochemical marker and as a higher throughput alternative to morphological endpoints such as head-trunk angle, tail length and morphological score. Embryos were exposed from 4 to 52 h post-fertilization (hpf) to a selection of known embryotoxic/teratogen compounds (valproic acid, retinoic acid, caffeine, sodium salicylate, glucose, hydroxyurea, methoxyacetic acid, boric acid and paraoxon-methyl) over a concentration range. They were evaluated for AChE activity, head-trunk angle, tail length and several qualitative parameters integrated in a morphological score. In general, the different patterns of the concentration-response curves allowed distinguishing between chemicals that produced growth retardation (valproic and methoxyacetic acid) and chemicals that produced non-growth-delay related malformations. An acceptable correlation between the morphological score, AChE activity and head-trunk angle as markers of developmental delay was observed, being AChE activity particularly sensitive to detect delay in the absence of malformations.
GRET-CERETOX and Toxicology Unit, Public Health Department, School of Pharmacy, University of Barcelona, Av Joan XXIII, E-08028 Barcelona, Spain. esterpique@ub.edu
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Teixidó
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Piqué
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Gómez-Catalán
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Llobet
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects* / Q000201:enzymology; D047108:Embryonic Development / Q000187:drug effects; D006257:Head / Q000002:abnormalities; D006330:Heart Defects, Congenital; D013623:Tail / Q000002:abnormalities; D013723:Teratogens / Q000633:toxicity*; D015027:Zebrafish / Q000002:abnormalities
D013723:Teratogens; D000110:Acetylcholinesterase