title: Developmental toxicity and brain aromatase induction by high genistein concentrations in zebrafish embryos.
abstract: Genistein is a phytoestrogen found at a high level in soybeans. In vitro and in vivo studies showed that high concentrations of genistein caused toxic effects. This study was designed to test the feasibility of zebrafish embryos for evaluating developmental toxicity and estrogenic potential of high genistein concentrations. The zebrafish embryos at 24 h post-fertilization were exposed to genistein (1 x 10(-4) M, 0.5 x 10(-4) M, 0.25 x 10(-4) M) or vehicle (ethanol, 0.1%) for 60 h. Genistein-treated embryos showed decreased heart rates, retarded hatching times, decreased body length, and increased mortality in a dose-dependent manner. After 0.25 x 10(-4) M genistein treatment, malformations of survived embryos such as pericardial edema, yolk sac edema, and spinal kyphosis were also observed. TUNEL assay results showed apoptotic DNA fragments in brain. This study also confirmed the estrogenic potential of genistein by EGFP expression in the brain of the mosaic reporter zebrafish embryos. This study first demonstrated that high concentrations of genistein caused a teratogenic effect on zebrafish embryos and confirmed the estrogenic potential of genistein in mosaic reporter zebrafish embryos.
authors.affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors.forename: Dong-Jae
authors.initials: DJ
authors.lastname: Kim
authors.forename: Seung-Hyeok
authors.initials: SH
authors.lastname: Seok
authors.forename: Min-Won
authors.initials: MW
authors.lastname: Baek
authors.forename: Hui-Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Yi-Rang
authors.initials: YR
authors.lastname: Na
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Hyun-Kyoung
authors.initials: HK
authors.lastname: Lee
authors.forename: Noton Kumar
authors.initials: NK
authors.lastname: Dutta
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawakami
authors.forename: Jae-Hak
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001141:Aromatase / Q000096:biosynthesis*; D001483:Base Sequence; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D017930:Genes, Reporter; D019833:Genistein / Q000633:toxicity*; D020287:In Situ Nick-End Labeling; D013723:Teratogens / Q000633:toxicity*; D018675:Toxicity Tests; D015027:Zebrafish / Q000196:embryology*
chemical_list: D017931:DNA Primers; D013723:Teratogens; D019833:Genistein; D001141:Aromatase