PUBLICATION

17beta-Estradiol inhibits chondrogenesis in the skull development of zebrafish embryos

Authors
Fushimi, S., Wada, N., Nohno, T., Tomita, M., Saijoh, K., Sunami, S., and Katsuyama, H.
ID
ZDB-PUB-090424-29
Date
2009
Source
Aquatic toxicology (Amsterdam, Netherlands)   95(4): 292-298 (Journal)
Registered Authors
Katsuyama, Hironobu
Keywords
17β-Estradiol (E2), Zebrafish, Chondrogenesis, Sonic hedgehog
MeSH Terms
  • Animals
  • Chondrogenesis/drug effects*
  • Embryo, Nonmammalian/abnormalities
  • Embryo, Nonmammalian/drug effects
  • Estradiol/toxicity*
  • Estrogens/toxicity*
  • Growth Inhibitors/toxicity
  • Hedgehog Proteins/metabolism*
  • Skull/abnormalities
  • Skull/drug effects*
  • Skull/embryology
  • Zebrafish/abnormalities
  • Zebrafish/embryology*
  • Zebrafish/metabolism
PubMed
19386370 Full text @ Aquat. Toxicol.
Abstract
17beta-Estradiol (E2) plays important roles in the development and differentiation of the gonad and central nervous systems, but little is known regarding the effects of exogenous E2 on chondrogenesis in skeletal development. In the present study, we found that treatment with E2 1-5 days post-fertilization (dpf) at concentrations above 1.5x10(-5)M increased the mortality rate in zebrafish embryos. Morphological analysis showed that treatment with E2 1-5dpf caused abnormal cartilage formation in a dose-dependent manner at concentrations above 5x10(-6)M. E2 1-5dpf at 1.5x10(-5)M caused defects of the ethmoid plate, parallel cleft of the trabecular cartilage, and hypoplasia of Meckel's cartilage and the ceratohyal cartilage. The sensitivity of embryos to E2 depended on the developmental stage. In early chondrogenesis (1-2dpf), the embryos were highly sensitive to E2, leading to hypoplasia of the cartilage. In situ hybridization studies showed that expression levels of patched1 (ptc1) and patched2 (ptc2) receptor mRNAs were markedly decreased by exposure to 2x10(-5)M E2 1-2dpf. However, the expression levels of sonic hedgehog (shh) and tiggywinkle hedgehog (twhh) mRNAs were constant in the E2-treated embryos. In addition, the estrogen receptor antagonist ICI 182,780 did not completely abolish the effects of E2, suggesting that E2 may not inhibit chondrogenesis through its nuclear estrogen receptor. These results suggest that exposure to exogenous E2 possibly inhibits chondrogenesis via inhibition of the hedgehog (Hh) signal transduction system.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping