PUBLICATION

Molecular targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) within the zebrafish ovary: Insights into TCDD-induced endocrine disruption and reproductive toxicity

Authors
Heiden, T.C., Struble, C.A., Rise, M.L., Hessner, M.J., Hutz, R.J., and Carvan, M.J. 3rd.
ID
ZDB-PUB-070924-6
Date
2008
Source
Reproductive toxicology (Elmsford, N.Y.)   25(1): 47-57 (Journal)
Registered Authors
Carvan III, Michael J., King Heiden, Tisha
Keywords
TCDD, Ovary, Zebrafish, Follicular development, Microarray, Endocrine disruptors
Datasets
GEO:GSE4859
MeSH Terms
  • Animals
  • Endocrine Disruptors/toxicity*
  • Estrogens/metabolism
  • Female
  • Gene Expression Profiling/methods
  • Gene Expression Regulation, Developmental/drug effects*
  • Gonadotropins/metabolism
  • Oligonucleotide Array Sequence Analysis
  • Ovarian Follicle/drug effects
  • Ovarian Follicle/metabolism
  • Ovary/drug effects*
  • Ovary/metabolism
  • Regulatory Sequences, Nucleic Acid/drug effects
  • Reproduction/drug effects*
  • Reproduction/genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction/drug effects*
  • Signal Transduction/genetics
  • Transcription, Genetic/drug effects
  • Zebrafish
PubMed
17884332 Full text @ Reprod. Toxicol.
CTD
17884332
Abstract
TCDD is a reproductive toxicant and endocrine disruptor, yet the mechanisms by which it causes these reproductive alterations are not fully understood. In order to provide additional insight into the molecular mechanisms that underlie TCDD's reproductive toxicity, we assessed TCDD-induced transcriptional changes in the ovary as they relate to previously described impacts on serum estradiol concentrations and altered follicular development in zebrafish. In silico computational approaches were used to correlate candidate regulatory motifs with observed changes in gene expression. Our data suggest that TCDD inhibits follicle maturation via attenuated gonadotropin responsiveness and/or depressed estradiol biosynthesis, and that interference of estrogen-regulated signal transduction may also contribute to TCDD's impacts on follicular development. TCDD may also alter ovarian function by disrupting various signaling pathways such as glucose and lipid metabolism, and regulation of transcription. Furthermore, events downstream from initial TCDD molecular-targets likely contribute to ovarian toxicity following chronic exposure to TCDD. Data presented here provide further insight into the mechanisms by which TCDD disrupts follicular development and reproduction in fish, and can be used to formulate new hypotheses regarding previously documented ovarian toxicity.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping