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Aop: 51

AOP Title

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PPARα activation leading to impaired fertility in adult male rodents

Short name:

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PPAR and reproductive toxicity

Graphical Representation

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Click to download graphical representation template

Authors

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

Point of Contact

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Elise Grignard   (email point of contact)

Contributors

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  • Elise Grignard

Status

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Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite Under Development 1.21 Included in OECD Work Plan


This AOP was last modified on June 06, 2017 08:36

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Revision dates for related pages

Page Revision Date/Time
impaired, Fertility December 02, 2016 09:21
Increase, Luteinizing hormone (LH) September 16, 2017 10:15
Hyperplasia, Leydig cell September 27, 2017 14:00
Increase proliferation, Leydig cell September 16, 2017 10:15
Activation, PPARα September 16, 2017 10:14
Reduction, testosterone level September 16, 2017 10:14
Reduction, Testosterone synthesis in Leydig cells September 16, 2017 10:14
Reduction, Cholesterol transport in mitochondria September 16, 2017 10:14
Increase proliferation, Leydig cell leads to Hyperplasia, Leydig cell December 03, 2016 16:37
Reduction, Testosterone synthesis in Leydig cells leads to Reduction, testosterone level December 02, 2016 10:18
Reduction, Cholesterol transport in mitochondria leads to Reduction, Testosterone synthesis in Leydig cells December 02, 2016 10:16
Reduction, testosterone level leads to Increase, Luteinizing hormone (LH) December 03, 2016 16:37
Increase, Luteinizing hormone (LH) leads to Increase proliferation, Leydig cell December 03, 2016 16:37
Hyperplasia, Leydig cell leads to impaired, Fertility December 03, 2016 16:37

Abstract

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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
1 MIE 227 Activation, PPARα Activation, PPARα
2 KE 414 Increase, Luteinizing hormone (LH) Increase, Luteinizing hormone (LH)
3 KE 415 Hyperplasia, Leydig cell Hyperplasia, Leydig cell
4 KE 416 Increase proliferation, Leydig cell Increase proliferation, Leydig cell
5 KE 446 Reduction, testosterone level Reduction, testosterone level
6 KE 413 Reduction, Testosterone synthesis in Leydig cells Reduction, Testosterone synthesis in Leydig cells
7 KE 447 Reduction, Cholesterol transport in mitochondria Reduction, Cholesterol transport in mitochondria
8 AO 406 impaired, Fertility impaired, Fertility

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Increase proliferation, Leydig cell leads to Hyperplasia, Leydig cell adjacent Moderate
Reduction, Testosterone synthesis in Leydig cells leads to Reduction, testosterone level adjacent High
Reduction, Cholesterol transport in mitochondria leads to Reduction, Testosterone synthesis in Leydig cells adjacent Moderate
Reduction, testosterone level leads to Increase, Luteinizing hormone (LH) non-adjacent Moderate
Increase, Luteinizing hormone (LH) leads to Increase proliferation, Leydig cell non-adjacent Moderate
Hyperplasia, Leydig cell leads to impaired, Fertility non-adjacent Moderate

Network View

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Stressors

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Life Stage Applicability

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Life stage Evidence
Adult, reproductively mature Moderate
Juvenile Moderate

Taxonomic Applicability

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Term Scientific Term Evidence Link
rat Rattus norvegicus 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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