Developmental toxicity and brain aromatase induction by high genistein concentrations in zebrafish embryos.
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.
Kim
Dong-Jae
DJ
Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
Seok
Seung-Hyeok
SH
Baek
Min-Won
MW
Lee
Hui-Young
HY
Na
Yi-Rang
YR
Park
Sung-Hoon
SH
Lee
Hyun-Kyoung
HK
Dutta
Noton Kumar
NK
Kawakami
Koichi
K
Park
Jae-Hak
JH
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*
D017931:DNA Primers; D013723:Teratogens; D019833:Genistein; D001141:Aromatase