PUBLICATION
Disruption of liver development and coagulation pathway by ochratoxin A in embryonic zebrafish
- Authors
- Wu, T.S., Lin, Y.T., Huang, Y.T., Cheng, Y.C., Yu, F.Y., Liu, B.H.
- ID
- ZDB-PUB-171225-2
- Date
- 2017
- Source
- Toxicology and applied pharmacology 340: 1-8 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Blood Coagulation/drug effects*
- Blood Coagulation/physiology
- Carcinogens/toxicity
- Cell Survival/drug effects
- Cell Survival/physiology
- Dose-Response Relationship, Drug
- Embryonic Development/drug effects*
- Embryonic Development/physiology
- Liver/drug effects*
- Liver/embryology*
- Liver/metabolism
- Ochratoxins/toxicity*
- Signal Transduction/drug effects*
- Signal Transduction/physiology
- Zebrafish
- PubMed
- 29274910 Full text @ Tox. App. Pharmacol.
- CTD
- 29274910
Citation
Wu, T.S., Lin, Y.T., Huang, Y.T., Cheng, Y.C., Yu, F.Y., Liu, B.H. (2017) Disruption of liver development and coagulation pathway by ochratoxin A in embryonic zebrafish. Toxicology and applied pharmacology. 340:1-8.
Abstract
Ochratoxin A (OTA) is a mycotoxin that is found in various food and feed products. The molecular mechanisms that are associated with OTA hepatotoxicity and teratogenicity have not been extensively elucidated in a developing organism. In this study, the transcriptomic profile of zebrafish embryos indicates that hemostasis and blood coagulation are the top two pathways affected by OTA. The treatment of embryos with OTA was able to decrease the expression of genes that encode coagulation factors and liver markers, including f7, f9b, cp and vtna. OTA also weakened the signal of liver-specific microRNA-122. OTA administration not only reduced the size of a developing embryonic liver, but also decreased the number of phosphorylated histone H3-positive cells by immunohistochemical staining. OTA suppressed the expression of hhex and prox1, two critical transcriptional factors during hepatoblast specification, in the developing liver, but did not alter the insulin signal in the pancreas. In vitro analysis with zebrafish liver (ZFL) cells indicated that OTA blocked the expression of f7, fgb and liver markers. In summary, OTA exposure resulted in the generation of small livers which led to deficiency of coagulation factors in embryonic zebrafish. Impairment of hhex and prox1 gene expression and hepatocyte proliferation contributed to the disruption of liver development mediated by OTA.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping