Zebrafish as a novel experimental model for developmental toxicology

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.

Retinal Neuronal Cell is a Toxicological Target of Tributyltin in Developing Zebrafish

“…This is reminiscent of findings that the retina as well as the corneal epithelium, lens, and pigment layer showed dose-dependent degenerative changes in TBT-and TPTexposed minnow larva [7,8]. In this investigation, we show that TBT preferentially induces apoptosis in retinal neuronal cells of developing zebrafish by way of oxidative stress, a model fish for developmental toxicology [25].…”

“…Our results highlight zebrafish embryos as a useful in vivo model system to study the molecular mechanisms of toxicity, including oxidative stress generated by organotin compounds. Microarray analysis might be useful to elucidate the mechanism of organotin toxicity [25]. Particularly, it is interesting to address which gene could be responsible for the zebrafish resistance against organotin.…”

“…Particularly, it is interesting to address which gene could be responsible for the zebrafish resistance against organotin. Gene-knockdown with morpholino origonucleotides should be powerful tool to study the role of candidate gene related to organotin toxicity [25]. TBT-binding protein, which has been identified in serum of Japanese flounder, is one of the candidates [22].…”

Pharmacology and toxicology of pahayokolide A, a bioactive metabolite from a freshwater species of Lyngbya isolated from the Florida Everglades

“…The zebrafish embryo is becoming an increasingly important model for studies in pharmacology (Parng et al, 2002) and vertebrate toxicology (Teraoka et al, 2003), as well as molecular biology (e.g., Malicki et al, 2002) and drug discovery (Moon et al, 2002).…”

Inhibition of spawning in zebrafish (Danio rerio): Adverse outcome pathways of quinacrine and ethinylestradiol

“…The zebrafish is widely used as a model species for vertebrate development studies and more recently has become embraced for use in the area of reproductive toxicology (Selderslaghs, Van Rompay, De Coen, & Witters, 2009;Alsop, Brown, & Van Der Kraak, 2007;Lister, Regan, Van Zwol, & Van Der Kraak, 2009). Large numbers of zebrafish can be housed in comparatively small spaces, which is beneficial as it is cost effective in terms of maintenance (Teraoka, Dong & Hiraga, 2003). Zebrafish have been utilized in a variety of scientific studies since the 1930's (Laale, 1977), which has resulted in a large amount of morphological, biochemical and physiological information, including a fully sequenced genome (Hill, Teraoka, Heideman, & Peterson, 2005).…”