Immediate and long-term consequences of vascular toxicity during zebrafish development.

Journal Article (Journal Article)

Proper formation of the vascular system is necessary for embryogenesis, and chemical disruption of vascular development may be a key event driving developmental toxicity. In order to test the effect of environmental chemicals on this critical process, we evaluated a quantitative assay in transgenic zebrafish using angiogenesis inhibitors that target VEGFR2 (PTK787) or EGFR (AG1478). Both PTK787 and AG1478 exposure impaired intersegmental vessel (ISV) sprouting, while AG1478 also produced caudal and pectoral fin defects at concentrations below those necessary to blunt ISV morphogenesis. The functional consequences of vessel toxicity during early development included decreased body length and survival in juvenile cohorts developmentally exposed to inhibitor concentrations sufficient to completely block ISV sprouting angiogenesis. These data show that concentration-dependent disruption of the presumed targets for these inhibitors produce adverse outcomes at advanced life stages.

Full Text

Duke Authors

Cited Authors

  • Tal, TL; McCollum, CW; Harris, PS; Olin, J; Kleinstreuer, N; Wood, CE; Hans, C; Shah, S; Merchant, FA; Bondesson, M; Knudsen, TB; Padilla, S; Hemmer, MJ

Published Date

  • September 2014

Published In

Volume / Issue

  • 48 /

Start / End Page

  • 51 - 61

PubMed ID

  • 24907688

Electronic International Standard Serial Number (EISSN)

  • 1873-1708

International Standard Serial Number (ISSN)

  • 0890-6238

Digital Object Identifier (DOI)

  • 10.1016/j.reprotox.2014.05.014


  • eng