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AOP: 323
Title
PPARalpha Agonism Impairs Fish Reproduction
Short name
Graphical Representation
Point of Contact
Contributors
- Ashley Kittelson
- John Hoang
- Robin Kutsi
- Jennifer Olker
Coaches
Status
Handbook Version | OECD status | OECD project |
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v2.0 |
This AOP was last modified on April 29, 2023 16:03
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Activation, PPARα | December 28, 2020 12:48 |
Decreased, cholesterol | May 24, 2022 11:10 |
Decreased, plasma 11-ketotestosterone level | May 24, 2022 13:51 |
Impaired, Spermatogenesis | May 16, 2022 02:14 |
Viable offspring, decreased | July 18, 2022 17:07 |
Decrease, Population growth rate | January 03, 2023 09:09 |
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 | April 19, 2021 13:32 |
Impaired, Spermatogenesis leads to Viable offspring, decreased | July 18, 2022 17:08 |
Viable offspring, decreased leads to Decrease, Population growth rate | July 18, 2022 17:09 |
Abstract
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.
AOP Development Strategy
Context
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
---|
MIE | 227 | Activation, PPARα | Activation, PPARα |
KE | 807 | Decreased, cholesterol | Decreased, cholesterol |
KE | 1756 | Decreased, plasma 11-ketotestosterone level | Decreased, 11KT |
KE | 1758 | Impaired, Spermatogenesis | Impaired, Spermatogenesis |
AO | 2032 | Viable offspring, decreased | Viable offspring, decreased |
AO | 360 | Decrease, Population growth rate | Decrease, Population growth rate |
Relationships Between Two Key Events (Including MIEs and AOs)
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 |
Impaired, Spermatogenesis leads to Viable offspring, decreased | adjacent | ||
Viable offspring, decreased leads to Decrease, Population growth rate | adjacent |
Network View
Prototypical Stressors
Life Stage Applicability
Life stage | Evidence |
---|---|
Adult | High |
Taxonomic Applicability
Term | Scientific Term | Evidence | Link |
---|---|---|---|
teleost fish | teleost fish | High | NCBI |
Sex Applicability
Sex | Evidence |
---|---|
Male | High |
Overall Assessment of the AOP
Domain of Applicability
Essentiality of the Key Events
Evidence Assessment
Known Modulating Factors
Modulating Factor (MF) | Influence or Outcome | KER(s) involved |
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