Dynamics in zebrafish development define transcriptomic specificity after angiogenesis inhibitor exposure.

Area of Science:

• Developmental toxicology
• Transcriptomics
• Zebrafish embryo model

Background:

• Current developmental toxicity testing is animal-intensive and costly.
• The zebrafish embryo offers a potential alternative model to reduce animal use and costs.
• Identifying specific biomarkers for developmental toxicity is crucial for regulatory assessment.

Purpose of the Study:

• To evaluate the potential of zebrafish embryo transcriptome analysis for identifying developmental toxicity biomarkers.
• To use anti-angiogenesis as a model to assess the specificity and sensitivity of transcriptomic responses.
• To compare early and late exposure scenarios for identifying key events in developmental toxicity.

Main Methods:

• Zebrafish embryos were exposed to tyrosine kinase inhibitors (sorafenib, SU4312) and rotenone.
• Time-resolved transcriptome analysis was performed at early (2 hours post fertilization) and late (24 hours post fertilization) stages.
• Generalized additive models (GAMs) were used to identify differentially expressed genes (DEGs).

Main Results:

• Early exposure resulted mainly in unspecific developmental toxicity.
• Specific repression of vascular-related genes was partially observed in early exposure but clearly identified in late exposure.
• Rotenone did not show an angiogenesis-specific transcriptomic response, suggesting observed effects were secondary.

Conclusions:

• Zebrafish embryo transcriptome analysis, particularly with late-stage exposure, can identify specific vascular-related gene expression changes.
• This model shows promise for supporting the identification of biomarkers for developmental toxicity, specifically anti-angiogenesis.
• The study highlights the importance of exposure timing in transcriptomic analysis for accurate toxicity assessment.