Developmental toxicity assay using high content screening of zebrafish embryos

Authors

  • Susan Lantz-McPeak,

    1. Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA
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  • Xiaoqing Guo,

    1. Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA
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  • Elvis Cuevas,

    1. Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA
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  • Melanie Dumas,

    1. Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA
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  • Glenn D. Newport,

    1. Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA
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  • Syed F. Ali,

    1. Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA
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  • Merle G. Paule,

    1. Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA
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  • Jyotshna Kanungo

    Corresponding author
    1. Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA
    • Correspondence to: Jyotshna Kanungo, Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, Bldg. 53D, Room 203O, Jefferson, AR 72079, USA. E-mail: jyotshnabala.kanungo@fda.hhs.gov

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Abstract

Typically, time-consuming standard toxicological assays using the zebrafish (Danio rerio) embryo model evaluate mortality and teratogenicity after exposure during the first 2 days post-fertilization. Here we describe an automated image-based high content screening (HCS) assay to identify the teratogenic/embryotoxic potential of compounds in zebrafish embryos in vivo. Automated image acquisition was performed using a high content microscope system. Further automated analysis of embryo length, as a statistically quantifiable endpoint of toxicity, was performed on images post-acquisition. The biological effects of ethanol, nicotine, ketamine, caffeine, dimethyl sulfoxide and temperature on zebrafish embryos were assessed. This automated developmental toxicity assay, based on a growth-retardation endpoint should be suitable for evaluating the effects of potential teratogens and developmental toxicants in a high throughput manner. This approach can significantly expedite the screening of potential teratogens and developmental toxicants, thereby improving the current risk assessment process by decreasing analysis time and required resources. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

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