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Aop: 103

AOP Title

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Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint

Short name:

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Cyclooxygenase inhibition 5

Graphical Representation

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Click to download graphical representation template

Authors

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Dalma Martinovic-Wegelt

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 Do not cite 1.29 Under Development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 July 17, 2018 17:47

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Revision dates for related pages

Page Revision Date/Time
Inhibition, Cyclooxygenase activity September 16, 2017 10:14
Reduced, Prostaglandin E2 concentration, hypothalamus September 16, 2017 10:15
Reduced, Gonadotropin releasing hormone, hypothalamus September 16, 2017 10:15
Reduced, Luteinizing hormone (LH), plasma September 16, 2017 10:15
Reduced, Maturation inducing steroid, plasma September 16, 2017 10:15
Reduced, Maturation inducing steroid receptor signalling, oocyte September 16, 2017 10:15
Upregulated, Spindle assembly checkpoint protein Mad2-oocyte September 16, 2017 10:15
Increased, Chromosome misseggregation September 16, 2017 10:15
Reduced, Reproductive Success December 03, 2016 16:37
Decrease, Population trajectory September 26, 2017 11:33
Inhibition, Cyclooxygenase activity leads to Reduced, Prostaglandin E2 concentration, hypothalamus December 03, 2016 16:37
Reduced, Prostaglandin E2 concentration, hypothalamus leads to Reduced, Gonadotropin releasing hormone, hypothalamus December 03, 2016 16:37
Reduced, Gonadotropin releasing hormone, hypothalamus leads to Reduced, Luteinizing hormone (LH), plasma December 03, 2016 16:37
Reduced, Luteinizing hormone (LH), plasma leads to Reduced, Maturation inducing steroid, plasma December 03, 2016 16:37
Reduced, Maturation inducing steroid, plasma leads to Reduced, Maturation inducing steroid receptor signalling, oocyte December 03, 2016 16:37
Reduced, Maturation inducing steroid receptor signalling, oocyte leads to Upregulated, Spindle assembly checkpoint protein Mad2-oocyte December 03, 2016 16:37
Upregulated, Spindle assembly checkpoint protein Mad2-oocyte leads to Increased, Chromosome misseggregation December 03, 2016 16:37
Increased, Chromosome misseggregation leads to Reduced, Reproductive Success December 03, 2016 16:37
Reduced, Reproductive Success leads to Decrease, Population trajectory 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 79 Inhibition, Cyclooxygenase activity Inhibition, Cyclooxygenase activity
2 KE 687 Reduced, Prostaglandin E2 concentration, hypothalamus Reduced, Prostaglandin E2 concentration, hypothalamus
3 KE 689 Reduced, Gonadotropin releasing hormone, hypothalamus Reduced, Gonadotropin releasing hormone, hypothalamus
4 KE 690 Reduced, Luteinizing hormone (LH), plasma Reduced, Luteinizing hormone (LH), plasma
5 KE 691 Reduced, Maturation inducing steroid, plasma Reduced, Maturation inducing steroid, plasma
6 KE 692 Reduced, Maturation inducing steroid receptor signalling, oocyte Reduced, Maturation inducing steroid receptor signalling, oocyte
7 KE 695 Upregulated, Spindle assembly checkpoint protein Mad2-oocyte Upregulated, Spindle assembly checkpoint protein Mad2-oocyte
8 KE 696 Increased, Chromosome misseggregation Increased, Chromosome misseggregation
9 AO 675 Reduced, Reproductive Success Reduced, Reproductive Success
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, Cyclooxygenase activity leads to Reduced, Prostaglandin E2 concentration, hypothalamus adjacent Moderate Low
Reduced, Prostaglandin E2 concentration, hypothalamus leads to Reduced, Gonadotropin releasing hormone, hypothalamus adjacent High Low
Reduced, Gonadotropin releasing hormone, hypothalamus leads to Reduced, Luteinizing hormone (LH), plasma adjacent High Moderate
Reduced, Luteinizing hormone (LH), plasma leads to Reduced, Maturation inducing steroid, plasma adjacent High Low
Reduced, Maturation inducing steroid, plasma leads to Reduced, Maturation inducing steroid receptor signalling, oocyte adjacent High Low
Reduced, Maturation inducing steroid receptor signalling, oocyte leads to Upregulated, Spindle assembly checkpoint protein Mad2-oocyte adjacent Low Low
Upregulated, Spindle assembly checkpoint protein Mad2-oocyte leads to Increased, Chromosome misseggregation adjacent Moderate Low
Increased, Chromosome misseggregation leads to Reduced, Reproductive Success adjacent High Moderate
Reduced, Reproductive Success leads to Decrease, Population trajectory adjacent Moderate Low

Network View

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Stressors

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Life Stage Applicability

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Life stage Evidence
Adult, reproductively mature High

Taxonomic Applicability

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Term Scientific Term Evidence Link
Human, rat, mouse Human, rat, mouse NCBI
goldfish Carassius auratus Low NCBI

Sex Applicability

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Sex Evidence
Female 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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