Aop:51

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Status

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

https://aopwiki.org/aops/51


AOP Title

PPARα activation leading to impaired fertility in adult male rodents
Short name: PPAR and reproductive toxicity

Authors

Malgorzata Nepelska, Sharon Munn, Brigitte Landesmann Systems Toxicology Unit, Institute for Health and Consumer Protection, Joint Research Centre, European Commission, Ispra, Varese, Italy

Status

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OECD Project 1.21: Three Adverse Outcome Pathways from Peroxisome Proliferator-Activated Receptors (PPARs) Activation Leading to Reproductive Toxicity in Rodents

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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
PPARα, Activation Weak

Key Events

Event Support for Essentiality
Luteinizing hormone (LH) , Increase Moderate
Leydig cell, Hyperplasia Moderate
Leydig cell , Increase proliferation Moderate
testosterone level, Reduction Moderate
Testosterone synthesis in Leydig cells, Reduction Moderate
Cholesterol transport in mitochondria, Reduction Weak

Adverse Outcome

Adverse Outcome
Fertility, impaired

Relationships Among Key Events and the Adverse Outcome

Event Description Triggers Weight of Evidence Quantitative Understanding
Cholesterol transport in mitochondria, Reduction Directly Leads to Testosterone synthesis in Leydig cells, Reduction Moderate
Testosterone synthesis in Leydig cells, Reduction Directly Leads to testosterone level, Reduction Strong
testosterone level, Reduction Indirectly Leads to Luteinizing hormone (LH) , Increase Moderate
Luteinizing hormone (LH) , Increase Indirectly Leads to Leydig cell , Increase proliferation Moderate
Leydig cell , Increase proliferation Directly Leads to Leydig cell, Hyperplasia Moderate
Leydig cell, Hyperplasia Indirectly Leads to Fertility, impaired Moderate

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Life Stage Applicability

Life Stage Evidence Links
Adult, reproductively mature Moderate
Juvenile Moderate

Taxonomic Applicability

Name Scientific Name Evidence Links
rat Rattus sp. Strong NCBI

Sex Applicability

Sex Evidence Links
Male 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

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Quantitative Considerations

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References