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Updated: May 25, 2026

Imaging and 3D Reconstruction of Cerebrovascular Structures in Embryonic Zebrafish
Published on: April 22, 2014
Caffeine treatment disturbs the angiogenesis of zebrafish embryos
Chien-Hung Yeh1, Yun-Feng Liao, Chao-Yuan Chang
1Graduate Institute of Life Sciences, Tamkang University, Tamsui, New Taipei City, Taiwan.
Abstract:
Caffeine is a widely consumed substance that occurs in numerous dietary sources, but teratogenic effects of caffeine intake during embryonic development are still not clear. In the present study, we used the zebrafish as a model to assess caffeine-induced toxicity on embryonic vascular development. A green fluorescent vascular endothelium transgenic line, Tg(fli1:egfp), was utilized for the sensitive detection of vascular development, including vasculo- and angiogenesis. Caffeine-treated embryos showed no defects in vasculogenesis, but revealed dose-dependent (250-350 ppm) developmental defects in intersegmental vessels, dorsal longitudinal anastomotic vessels, and subintestinal vein sprouting. Further, real-time polymerase chain reaction analysis of caffeine-treated embryos showed an upregulation of nrp1a along with a downregulation of sema3aa and sema3c. In conclusion, caffeine treatment induces defects of angiogenesis in zebrafish embryos.
Insights
Caffeine intake during embryonic development can cause vascular defects. This study in zebrafish embryos revealed dose-dependent impacts on blood vessel formation, highlighting potential risks.
Area of Science:
- Developmental Biology
- Toxicology
- Genetics
Background:
- Caffeine is a common dietary substance with unclear teratogenic effects on embryonic development.
- Understanding caffeine's impact on embryonic vascularization is crucial for public health.
Purpose of the Study:
- To investigate caffeine-induced toxicity on embryonic vascular development using zebrafish.
- To assess the effects of caffeine on vasculogenesis and angiogenesis in a model organism.
Main Methods:
- Utilized a green fluorescent vascular endothelium transgenic zebrafish line (Tg(fli1:egfp)) for sensitive detection.
- Administered varying doses of caffeine to zebrafish embryos.
- Analyzed vascular development, including intersegmental vessels, dorsal longitudinal anastomotic vessels, and subintestinal vein sprouting.
- Performed real-time polymerase chain reaction to analyze gene expression changes.
Main Results:
- Caffeine treatment did not affect vasculogenesis but caused dose-dependent defects in angiogenesis.
- Specific defects were observed in intersegmental vessels, dorsal longitudinal anastomotic vessels, and subintestinal vein sprouting at 250-350 ppm caffeine.
- Gene expression analysis revealed upregulation of nrp1a and downregulation of sema3aa and sema3c in caffeine-treated embryos.
Conclusions:
- Caffeine exposure during embryonic development in zebrafish leads to significant defects in angiogenesis.
- The findings suggest caffeine's potential to disrupt complex vascular network formation.
- Gene expression changes in nrp1a, sema3aa, and sema3c may underlie caffeine-induced vascular developmental abnormalities.

