PUBLICATION

Thyroid Hormone Disruptors Interfere with Molecular Pathways of Eye Development and Function in Zebrafish

Authors
Baumann, L., Segner, H., Ros, A., Knapen, D., Vergauwen, L.
ID
ZDB-PUB-190403-2
Date
2019
Source
International Journal of Molecular Sciences   20(7): (Journal)
Registered Authors
Knapen, Dries, Vergauwen, Lucia
Keywords
PTU, TBBPA, microarray, mode of action, pathways of toxicity, transcriptome analyses
Datasets
GEO:GSE121338, GEO:GSE121336, GEO:GSE121334
MeSH Terms
  • Animals
  • Down-Regulation/drug effects
  • Down-Regulation/genetics
  • Endocrine Disruptors/toxicity*
  • Eye/drug effects
  • Eye/embryology*
  • Gene Expression Profiling
  • Polybrominated Biphenyls/toxicity
  • Propylthiouracil/toxicity
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Thyroid Hormones/toxicity*
  • Transcription, Genetic/drug effects
  • Up-Regulation/drug effects
  • Up-Regulation/genetics
  • Zebrafish/metabolism*
PubMed
30934780 Full text @ Int. J. Mol. Sci.
Abstract
The effects of thyroid hormone disrupting chemicals (THDCs) on eye development of zebrafish were investigated. We expected THDC exposure to cause transcriptional changes of vision-related genes, which find their phenotypic anchoring in eye malformations and dysfunction, as observed in our previous studies. Zebrafish were exposed from 0 to 5 days post fertilization (dpf) to either propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, or tetrabromobisphenol-A (TBBPA), which interacts with thyroid hormone receptors. Full genome microarray analyses of RNA isolated from eye tissue revealed that the number of affected transcripts was substantially higher in PTU- than in TBBPA-treated larvae. However, multiple components of phototransduction (e.g., phosphodiesterase, opsins) were responsive to both THDC exposures. Yet, the response pattern for the gene ontology (GO)-class "sensory perception" differed between treatments, with over 90% down-regulation in PTU-exposed fish, compared to over 80% up-regulation in TBBPA-exposed fish. Additionally, the reversibility of effects after recovery in clean water for three days was investigated. Transcriptional patterns in the eyes were still altered and partly overlapped between 5 and 8 dpf, showing that no full recovery occurred within the time period investigated. However, pathways involved in repair mechanisms were significantly upregulated, which indicates activation of regeneration processes.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping