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Rapid Evaluation of Toxicity of Chemical Compounds Using Zebrafish Embryos
Published on: August 25, 2019
Zebrafish as a novel experimental model for developmental toxicology
Hiroki Teraoka1, Wu Dong, Takeo Hiraga
1Department of Toxicology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu 069-8501, Japan. hteraoka@rakuno.ac.jp
Abstract:
It is widely believed that embryos and infants during development are highly sensitive to chemicals that cause serious damage to growth. However, knowledge on the mechanisms of developmental toxicity is scarce. One reason for this is limited convenient model system other than organ cultures using rodents to study the various aspects of developmental toxicology. Cultured cells are not always adequate for this purpose, since events in morphogenesis are processed through interactions with other tissues. We focused on zebrafish embryo (Danio rerio), one of the most important organisms in developmental biology. Saturation mutagenesis, applied to drosophila and nematode to define the functions of genes, has been carried out in zebrafish but almost no other vertebrate, and several thousand lines are available due to the rapid growth and transparent body of this embryo. Enhanced databases for the genome and ESTs are available at websites with abundant genetic and biological background. By targeted gene knock-down with morpholino-modified antisense oligonucleotieds (morpholinos), the translation of a specific protein can be transiently blocked for several days. Many reporter systems in vivo have been established mainly as GFP-transgenic fish for environmental chemicals. Although several excellent studies have been performed with zebrafish embryos on the effects of chemicals, the developmental toxicology of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been most extensively studied to date. We have found that TCDD induces apoptosis in dorsal midbrain with a concomitant decrease in local blood flow, using developing zebrafish. TCDD seems to produce oxidative stress through CYP1A induction in vascular endothelium, resulting in local circulation failure and apoptosis in the dorsal midbrain. In addition to applications in toxicology, an experimental system with zebrafish embryos could help to clarify the mechanism of congenital anomaly, which arises from genetic mutation.
Insights
Zebrafish embryos reveal that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes developmental toxicity by inducing oxidative stress, leading to apoptosis in the dorsal midbrain and reduced blood flow.
Area of Science:
- Developmental toxicology
- Comparative toxicology
- Embryonic development research
Background:
- Embryos and infants are sensitive to developmental toxicants, but mechanisms are poorly understood.
- Rodent organ cultures and cell cultures have limitations for studying complex developmental processes.
- Zebrafish embryos offer a convenient vertebrate model due to rapid growth, transparency, and genetic resources.
Purpose of the Study:
- To investigate the developmental toxicity mechanisms of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) using zebrafish embryos.
- To explore the utility of zebrafish as a model for developmental toxicology and congenital anomaly research.
Main Methods:
- Utilized zebrafish embryos (Danio rerio) as a model system.
- Employed targeted gene knock-down using morpholino-modified antisense oligonucleotides.
- Investigated the effects of TCDD exposure on embryonic development, focusing on apoptosis and blood flow.
Main Results:
- TCDD exposure induced apoptosis in the dorsal midbrain of zebrafish embryos.
- A decrease in local blood flow was observed concurrently with TCDD-induced apoptosis.
- TCDD appears to cause oxidative stress via CYP1A induction in vascular endothelium, leading to circulation failure and apoptosis.
Conclusions:
- Zebrafish embryos are a valuable model for studying the mechanisms of developmental toxicity, including TCDD effects.
- TCDD-induced oxidative stress and subsequent circulatory failure contribute to dorsal midbrain apoptosis.
- This model system can advance understanding of congenital anomalies and chemical impacts on development.
