API XML

Aop: 323

AOP Title

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PPARalpha Agonism Impairs Fish Reproduction

Short name:

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PPARa Agonism Impairs Fish Reproduction

Graphical Representation

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Click to download graphical representation template

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Authors

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Ashley Kittelson, ORISE participant at US Environmental Protection Agency

Point of Contact

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Ashley Kittelson   (email point of contact)

Contributors

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  • Ashley Kittelson

Status

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Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite


This AOP was last modified on May 11, 2020 16:37

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Revision dates for related pages

Page Revision Date/Time
Activation, PPARα September 16, 2017 10:14
Decreased, cholesterol May 19, 2020 12:38
Decreased, 11-ketotestosterone May 19, 2020 12:29
Impaired, Spermatogenesis May 19, 2020 12:25
Activation, PPARα leads to Decreased, cholesterol May 01, 2020 11:10
Decreased, cholesterol leads to Decreased, 11KT May 06, 2020 09:31
Decreased, 11KT leads to Impaired, Spermatogenesis May 19, 2020 12:43

Abstract

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Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor. Along with retinoid x receptor (RXR) and a ligand, it promotes transcription of many genes including those involve in fatty acid β-oxidation and cholesterol metabolism. Fibrates are synthetic ligands of PPARα prescribed to lower cholesterol in humans. In fish this decrease in cholesterol causes a decrease in reproductive hormones, notably 11-ketotestosterone. This impairs the fish’s ability to reproduce. Fibrates’ effects on fish are relevant as they’re present in the environment.  


Background (optional)

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Summary of the AOP

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Events: Molecular Initiating Events (MIE)

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Key Events (KE)

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Adverse Outcomes (AO)

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Sequence Type Event ID Title Short name
MIE 227 Activation, PPARα Activation, PPARα
KE 807 Decreased, cholesterol Decreased, cholesterol
KE 1756 Decreased, 11-ketotestosterone Decreased, 11KT
KE 1758 Impaired, Spermatogenesis Impaired, Spermatogenesis

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Activation, PPARα leads to Decreased, cholesterol adjacent High Not Specified
Decreased, cholesterol leads to Decreased, 11KT adjacent High Not Specified
Decreased, 11KT leads to Impaired, Spermatogenesis adjacent High Not Specified

Network View

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Stressors

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Life Stage Applicability

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Life stage Evidence
Adult High

Taxonomic Applicability

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Term Scientific Term Evidence Link
teleost fish teleost fish High NCBI

Sex Applicability

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Sex Evidence
Male High

Overall Assessment of the AOP

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Domain of Applicability

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Essentiality of the Key Events

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Evidence Assessment

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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

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