PUBLICATION
Chemical-induced heart defects using a transgenic zebrafish model
- Authors
- Liu, S., Kawanishi, T., Shimada, A., Nukada, Y., Miyazawa, M., Takeda, H., Tasaki, J.
- ID
- ZDB-PUB-250613-3
- Date
- 2025
- Source
- Toxicological sciences : an official journal of the Society of Toxicology : (Journal)
- Registered Authors
- Shimada, Atsuko, Takeda, Hiroyuki
- Keywords
- Cardiomyocyte, Cardiotoxicity, Endocardium, Heart defects, Teratogen, Transgenic zebrafish model
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Disease Models, Animal
- Embryo, Nonmammalian/drug effects
- Genes, Reporter
- Heart*/drug effects
- Heart*/embryology
- Heart Defects, Congenital*/chemically induced
- Heart Defects, Congenital*/embryology
- Heart Defects, Congenital*/genetics
- Teratogens*/toxicity
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish Proteins/genetics
- PubMed
- 40504024 Full text @ Toxicol. Sci.
- CTD
- 40504024
Citation
Liu, S., Kawanishi, T., Shimada, A., Nukada, Y., Miyazawa, M., Takeda, H., Tasaki, J. (2025) Chemical-induced heart defects using a transgenic zebrafish model. Toxicological sciences : an official journal of the Society of Toxicology. :.
Abstract
Congenital heart defects (CHDs) are common birth defects attributed to genetic and environmental factors such as pharmaceuticals and chemicals. Identifying modifiable environmental factors and understanding their impact on heart development is crucial for mitigating chemical-induced CHDs. Given the increasing number of chemical agents, efficient high-throughput systems are essential to evaluate their teratogenic potential during cardiovascular development, which is a major concern for chemical safety. In this study, we developed three transgenic zebrafish reporter lines, myl7: EGFP, kdrl: MRFP and gata1: MKate2, which enable real-time visualization of myocardial and endocardial development and cardiac function based on blood flow. These transgenic embryos were used to investigate the teratogenic effects of chemicals well known to induce heart defects in mammals, including humans. Our real-time imaging revealed that the teratogens induced significant malformations in cardiac morphogenesis, including abnormal heart tube formation, incomplete cardiac looping, and reduced heart chamber size. These teratogens also disrupted the expression of cardiac progenitor markers, suggesting impaired cardiac progenitor development. These defects were detected at the early stages (4-48 hours post-fertilization), suggesting that the stages of progenitor development to heart looing were most susceptible to teratogen exposure, ie the critical period for teratogen-induced heart defects. Functional defects, such as impaired blood flow, were observed using real-time imaging of the gata1-reporter line. This study demonstrates the utilization of transgenic zebrafish embryo models for high-throughput teratogenicity testing, which also allows us to analyze the mechanisms underlying chemical-induced heart defects. Therefore, our zebrafish models would contribute to the identification and reduction of risks associated with CHDs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping