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

Area of Science:

• Developmental toxicology
• Vascular biology
• Zebrafish models

Background:

• Vascular system formation is crucial for embryogenesis.
• Chemical disruption of vascular development can cause developmental toxicity.
• A quantitative assay is needed to assess environmental chemical effects on vascular development.

Purpose of the Study:

• To evaluate a quantitative assay in transgenic zebrafish for assessing the effects of environmental chemicals on vascular development.
• To investigate the impact of angiogenesis inhibitors targeting VEGFR2 (PTK787) and EGFR (AG1478) on vascular development in zebrafish.

Main Methods:

• Utilized transgenic zebrafish embryos.
• Administered angiogenesis inhibitors PTK787 (VEGFR2 inhibitor) and AG1478 (EGFR inhibitor).
• Quantitatively assessed intersegmental vessel (ISV) sprouting and fin development.

Main Results:

• Both PTK787 and AG1478 exposure impaired ISV sprouting.
• AG1478 caused caudal and pectoral fin defects at sub-morphogenesis-blocking concentrations.
• Developmental exposure to inhibitors resulted in decreased body length and survival in juvenile zebrafish.

Conclusions:

• Concentration-dependent disruption of VEGFR2 and EGFR targets by environmental chemicals leads to adverse outcomes.
• The zebrafish assay effectively models chemical-induced vascular toxicity with functional consequences.
• This study highlights the link between early-life vascular disruption and later-life health effects.