title: Developmental toxicity assay using high content screening of zebrafish embryos.
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.
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Lantz-McPeak
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Guo
authors.forename: Elvis
authors.initials: E
authors.lastname: Cuevas
authors.forename: Melanie
authors.initials: M
authors.lastname: Dumas
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Newport
authors.forename: Syed F
authors.initials: SF
authors.lastname: Ali
authors.forename: Merle G
authors.initials: MG
authors.lastname: Paule
authors.forename: Jyotshna
authors.initials: J
authors.lastname: Kanungo
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000473:pathology; D047108:Embryonic Development / Q000187:drug effects*; D057166:High-Throughput Screening Assays / Q000379:methods*; D007091:Image Processing, Computer-Assisted; D013723:Teratogens / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods*; D015027:Zebrafish / Q000196:embryology*
chemical_list: D013723:Teratogens
keywords: automated imaging; ethanol; high content screening; integrated morphometric analysis; ketamine; nicotine; zebrafish embryo