Aop:122

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Status

This is a legacy representation of this AOP. Please see the current version here:

https://aopwiki.org/aops/122


AOP Title

Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation
Short name: Prolyl hydroxylase inhibition

Authors

Dalma Martinovic-Weigelt

Status

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OECD Project 1.29: A catalog of putative AOPs that will enhance the utility of US EPA Toxcast high throughput screening data for hazard identification

Under development: Do not distribute or cite.

This AOP page was last modified on 12/11/2016.

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Abstract

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Summary of the AOP

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Molecular Initiating Event

Molecular Initiating Event Support for Essentiality
Prolyl hydroxylases, Inhibition Moderate

Key Events

Event Support for Essentiality
HIF-1 heterodimer, Increased Moderate
Aromatase (Cyp19a1) mRNA, Decreased Weak
17beta-estradiol synthesis by ovarian granulosa cells, Reduction Moderate
Plasma 17beta-estradiol concentrations, Reduction Moderate
Vitellogenin synthesis in liver, Reduction Moderate
Plasma vitellogenin concentrations, Reduction Moderate
Vitellogenin accumulation into oocytes and oocyte growth/development, Reduction Moderate

Adverse Outcome

Adverse Outcome
Cumulative fecundity and spawning, Reduction
Population trajectory, Decrease

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
Prolyl hydroxylases, Inhibition Directly Leads to HIF-1 heterodimer, Increased Strong Weak
HIF-1 heterodimer, Increased Directly Leads to Aromatase (Cyp19a1) mRNA, Decreased Moderate Weak
Aromatase (Cyp19a1) mRNA, Decreased Directly Leads to 17beta-estradiol synthesis by ovarian granulosa cells, Reduction Strong Moderate
17beta-estradiol synthesis by ovarian granulosa cells, Reduction Directly Leads to Plasma 17beta-estradiol concentrations, Reduction Strong Moderate
Plasma 17beta-estradiol concentrations, Reduction Directly Leads to Vitellogenin synthesis in liver, Reduction Strong Moderate
Vitellogenin synthesis in liver, Reduction Directly Leads to Plasma vitellogenin concentrations, Reduction Strong Strong
Plasma vitellogenin concentrations, Reduction Directly Leads to Vitellogenin accumulation into oocytes and oocyte growth/development, Reduction Moderate
Vitellogenin accumulation into oocytes and oocyte growth/development, Reduction Directly Leads to Cumulative fecundity and spawning, Reduction
Cumulative fecundity and spawning, Reduction Directly Leads to Population trajectory, Decrease

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Life Stage Applicability

Life Stage Evidence Links
Adult, reproductively mature

Taxonomic Applicability

Name Scientific Name Evidence Links
Pimephales promelas Pimephales promelas NCBI

Sex Applicability

Sex Evidence Links
Female

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Overall Assessment of the AOP

Domain of Applicability

Life Stage Applicability, Taxonomic Applicability, Sex Applicability
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Essentiality of the Key Events

Molecular Initiating Event Summary, Key Event Summary
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Weight of Evidence Summary

Summary Table
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Quantitative Considerations

Summary Table
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Considerations for Potential Applications of the AOP (optional)

References