Benomyl induction of brain aromatase and toxic effects in the zebrafish embryo

Kim, D.J., Seok, S.H., Baek, M.W., Lee, H.Y., Na, Y.R., Park, S.H., Lee, H.K., Dutta, N.K., Kawakami, K., and Park, J.H.
Journal of applied toxicology : JAT   29(4): 289-294 (Journal)
Registered Authors
Kawakami, Koichi
benomyl, toxicity, zebrafish embryo, brain aromatase, EGFP
MeSH Terms
  • Animals
  • Aromatase/biosynthesis*
  • Aromatase/genetics
  • Benomyl/toxicity*
  • Brain/drug effects
  • Brain/enzymology*
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/physiology*
  • Fungicides, Industrial/toxicity*
  • Green Fluorescent Proteins/biosynthesis
  • Green Fluorescent Proteins/genetics
  • Heart Rate/drug effects
  • Microinjections
  • Plasmids/genetics
  • Survival Analysis
  • Teratogens/toxicity
  • Transposases/biosynthesis
  • Transposases/genetics
  • Zebrafish/physiology*
19058295 Full text @ J. Appl. Toxicol.
Benomyl is a benzimidazole fungicide that has been widely used on a variety of food crops and ornamental plants. It is known to cause adverse effects on reproductive systems, including decreased testicular and epididymal weights and reduced epididymal sperm counts and fertility. The brain aromatase gene is up-regulated by estrogens and estrogen mimics and considered a target gene to screen estrogen mimics. This study was designed to test the estrogenic potential and toxic effects of benomyl in the zebrafish system, and validated this system as a model that may correspond to the effect of benomyl in rodents. Concentrations of 20 x 10(-6), 40 x 10(-6) and 80 x 10(-6) m of benomyl-treated embryos showed decreased survival, hatching and heart rates, and increased incidence of malformations, such as pericardial edema, spinal lordosis, elongated heart, head edema, eye lens protrusion and caudal fin disappearance. Benomyl induced enhanced green fluorescent protein (EGFP) expression in the mediobasal hypothalamus (MBH) in transient zebrafish embryos with a brain aromatase-based reporter gene. In this study, we determined that benomyl has estrogenic potential based on zebrafish brain aromatase gene induction, and that benomyl is toxic at 20 x 10(-6) m concentration and higher. These results demonstrate the usefulness of zebrafish embryos as an in vivo system to examine the estrogenic and developmental toxic potential of unknown compounds.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes