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Aop: 122

AOP Title

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Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation

Short name:

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Prolyl hydroxylase inhibition

Graphical Representation

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Click to download graphical representation template

Authors

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Dalma Martinovic-Weigelt

Point of Contact

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Dalma Martinovic-Weigelt   (email point of contact)

Contributors

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  • Dalma Martinovic-Weigelt

Status

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Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite 1.29 Under Development


This AOP was last modified on January 27, 2018 15:34

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Revision dates for related pages

Page Revision Date/Time
Inhibition, Prolyl hydroxylases December 03, 2016 16:37
Increased, HIF-1 heterodimer December 03, 2016 16:37
Decreased, Aromatase (Cyp19a1) mRNA September 16, 2017 10:16
Reduction, 17beta-estradiol synthesis by ovarian granulosa cells September 16, 2017 10:14
Reduction, Plasma 17beta-estradiol concentrations September 26, 2017 11:30
Reduction, Vitellogenin synthesis in liver September 16, 2017 10:16
Reduction, Plasma vitellogenin concentrations September 16, 2017 10:14
Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development September 16, 2017 10:14
Reduction, Cumulative fecundity and spawning March 20, 2017 17:52
Decrease, Population trajectory September 26, 2017 11:33
Inhibition, Prolyl hydroxylases leads to Increased, HIF-1 heterodimer December 03, 2016 16:38
Increased, HIF-1 heterodimer leads to Decreased, Aromatase (Cyp19a1) mRNA December 03, 2016 16:38
Decreased, Aromatase (Cyp19a1) mRNA leads to Reduction, 17beta-estradiol synthesis by ovarian granulosa cells December 03, 2016 16:38
Reduction, 17beta-estradiol synthesis by ovarian granulosa cells leads to Reduction, Plasma 17beta-estradiol concentrations March 20, 2017 12:05
Reduction, Plasma 17beta-estradiol concentrations leads to Reduction, Vitellogenin synthesis in liver March 20, 2017 12:28
Reduction, Vitellogenin synthesis in liver leads to Reduction, Plasma vitellogenin concentrations March 20, 2017 12:58
Reduction, Plasma vitellogenin concentrations leads to Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development March 20, 2017 13:21
Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development leads to Reduction, Cumulative fecundity and spawning March 20, 2017 13:35
Reduction, Cumulative fecundity and spawning leads to Decrease, Population trajectory March 20, 2017 13:49

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 798 Inhibition, Prolyl hydroxylases Inhibition, Prolyl hydroxylases
2 KE 799 Increased, HIF-1 heterodimer Increased, HIF-1 heterodimer
3 KE 800 Decreased, Aromatase (Cyp19a1) mRNA Decreased, Aromatase (Cyp19a1) mRNA
4 KE 3 Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
5 KE 219 Reduction, Plasma 17beta-estradiol concentrations Reduction, Plasma 17beta-estradiol concentrations
6 KE 285 Reduction, Vitellogenin synthesis in liver Reduction, Vitellogenin synthesis in liver
7 KE 221 Reduction, Plasma vitellogenin concentrations Reduction, Plasma vitellogenin concentrations
8 KE 309 Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development
9 AO 78 Reduction, Cumulative fecundity and spawning Reduction, Cumulative fecundity and spawning
10 AO 360 Decrease, Population trajectory Decrease, Population trajectory

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Inhibition, Prolyl hydroxylases leads to Increased, HIF-1 heterodimer adjacent High Low
Increased, HIF-1 heterodimer leads to Decreased, Aromatase (Cyp19a1) mRNA adjacent Moderate Low
Decreased, Aromatase (Cyp19a1) mRNA leads to Reduction, 17beta-estradiol synthesis by ovarian granulosa cells adjacent High Moderate
Reduction, 17beta-estradiol synthesis by ovarian granulosa cells leads to Reduction, Plasma 17beta-estradiol concentrations adjacent High Moderate
Reduction, Plasma 17beta-estradiol concentrations leads to Reduction, Vitellogenin synthesis in liver adjacent High Moderate
Reduction, Vitellogenin synthesis in liver leads to Reduction, Plasma vitellogenin concentrations adjacent High High
Reduction, Plasma vitellogenin concentrations leads to Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development adjacent Moderate
Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development leads to Reduction, Cumulative fecundity and spawning adjacent
Reduction, Cumulative fecundity and spawning leads to Decrease, Population trajectory adjacent

Network View

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Stressors

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Life Stage Applicability

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Life stage Evidence
Adult, reproductively mature

Taxonomic Applicability

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Term Scientific Term Evidence Link
Pimephales promelas Pimephales promelas NCBI

Sex Applicability

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Sex Evidence
Female

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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