API

Relationship: 128

Title

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Agonism, Estrogen receptor leads to Increase, Vitellogenin synthesis in liver

Upstream event

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Agonism, Estrogen receptor

Downstream event

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Increase, Vitellogenin synthesis in liver

Key Event Relationship Overview

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AOPs Referencing Relationship

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AOP Name Directness Weight of Evidence Quantitative Understanding
Estrogen receptor agonism leading to reproductive dysfunction directly leads to Strong

Taxonomic Applicability

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Term Scientific Term Evidence Link
zebrafish Danio rerio Strong NCBI
fathead minnow Pimephales promelas Strong NCBI

Sex Applicability

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Life Stage Applicability

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How Does This Key Event Relationship Work

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Weight of Evidence

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Biological Plausibility

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High degree of plausibility in fathead minnow, zebrafish and other cyprinid species.

Empirical Support for Linkage

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A wide range of studies using adult fish show that induction of plasma vitellogenin (VTG) occurs within 21 days in vivo aquatic exposure to estrogen receptor agonists (eg 17beta-estradiol and 4-tert pentylphenol) as shown during the successful validation of the OECD Test Guideline 229 and related protocols. A smaller number of experiment studies with fish have shown that within the OECD Test Guideline 2010, larval fish can also show induction of whole body VTG levels within 21 days aquatic exposure to estrogen receptor agonists.

Uncertainties or Inconsistencies

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There are generally few inconsistencies for experimental studies using model fish species dervied from pathogen-free laboratory cultures. However, there can some uncertainties where wild fish have been used for experimental purposes.

Quantitative Understanding of the Linkage

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Evidence Supporting Taxonomic Applicability

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References

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Navas, J.M., Segner, H. (2006) Vitellogenin synthesis in primary cultures of fish liver cells as endpoint for in vitro screening of the (anti)estrogenic activity of chemical substances. Aquatic Toxicology 80: 1-22

Thorpe, K.L., Benstead, R., Hutchinson, T.H., Tyler, C.R. (2007). Associations between altered vitellogenin concentrations and adverse health effects in fathead minnow (Pimephales promelas). Aquatic Toxicology 85: 176-183