Aop:102

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Status

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

https://aopwiki.org/aops/102


AOP Title

Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition
Short name: Cyclooxygenase inhibition

Authors

Dalma Martinovic-Weigelt

Status

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

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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
Cyclooxygenase activity, Inhibition Moderate

Key Events

Event Support for Essentiality
Prostaglandin E2 concentration, hypothalamus, Reduced Moderate
Gonadotropin releasing hormone, hypothalamus, Reduced Moderate
Luteinizing hormone (LH), plasma , Reduced Weak
Maturation inducing steroid, plasma, Reduced Weak
Maturation inducing steroid receptor signalling, oocyte, Reduced Weak
Meiotic prophase I/metaphase I transition, oocyte, Reduced Weak
cyclic adenosine monophosphate, Increased Weak

Adverse Outcome

Adverse Outcome
Population trajectory, Decline
Reproductive Success, Reduced

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
Cyclooxygenase activity, Inhibition Directly Leads to Prostaglandin E2 concentration, hypothalamus, Reduced Moderate Weak
Prostaglandin E2 concentration, hypothalamus, Reduced Directly Leads to Gonadotropin releasing hormone, hypothalamus, Reduced Strong Weak
Gonadotropin releasing hormone, hypothalamus, Reduced Directly Leads to Luteinizing hormone (LH), plasma , Reduced Strong Moderate
Luteinizing hormone (LH), plasma , Reduced Directly Leads to Maturation inducing steroid, plasma, Reduced Strong Weak
Maturation inducing steroid, plasma, Reduced Directly Leads to Maturation inducing steroid receptor signalling, oocyte, Reduced Strong Weak
Maturation inducing steroid receptor signalling, oocyte, Reduced Directly Leads to cyclic adenosine monophosphate, Increased Moderate Weak
cyclic adenosine monophosphate, Increased Directly Leads to Meiotic prophase I/metaphase I transition, oocyte, Reduced Strong Weak
Meiotic prophase I/metaphase I transition, oocyte, Reduced Directly Leads to Reproductive Success, Reduced Strong Weak
Reproductive Success, Reduced Directly Leads to Population trajectory, Decline Strong Strong

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Life Stage Applicability

Life Stage Evidence Links
Adult, reproductively mature Strong

Taxonomic Applicability

Name Scientific Name Evidence Links
Human, rat, mouse
goldfish Carassius auratus Weak NCBI

Sex Applicability

Sex Evidence Links
Female Strong

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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