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Aop: 310

AOP Title

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Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR

Short name:

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AHR mediated epigenetic reproductive failure

Graphical Representation

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Click to download graphical representation template

Authors

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Jon Doering, Ph.D., University of Lethbridge, Lethbridge, AB, Canada (jad929@mail.usask.ca)

Prof. Steve Wiseman, Ph.D., University of Lethbridge, Lethbridge, AB, Canada (steve.wiseman@uleth.ca)

Point of Contact

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Jon Doering   (email point of contact)

Contributors

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  • Jon Doering

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 Do not cite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 October 30, 2019 16:55

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Revision dates for related pages

Page Revision Date/Time
Activation, AhR March 22, 2018 14:00
Increase, DNA methyltransferase expression October 30, 2019 16:13
Increase, hypermethylation of the promotor region of gonadotropin releasing hormone receptor October 30, 2019 16:15
Decrease, expression of gonadotropin releasing hormone receptor October 30, 2019 16:15
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
dimerization, AHR/ARNT September 16, 2017 10:14
Reduction, Cumulative fecundity and spawning March 20, 2017 17:52
Decrease, Population trajectory September 26, 2017 11:33
Activation, AhR leads to dimerization, AHR/ARNT March 22, 2018 11:02
Reduction, Plasma 17beta-estradiol concentrations leads to Reduction, Plasma vitellogenin concentrations October 18, 2018 11:02
dimerization, AHR/ARNT leads to Increase, DNMT expression October 30, 2019 16:34
Increase, DNMT expression leads to Increase, hypermethylation of the promotor region of GnRHR October 30, 2019 16:25
Increase, hypermethylation of the promotor region of GnRHR leads to Decease, expression of GnRHR October 30, 2019 16:25
Decease, expression of GnRHR leads to Reduction, 17beta-estradiol synthesis by ovarian granulosa cells October 30, 2019 16:26
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
benzo[a]pyrene October 30, 2019 16:47

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 18 Activation, AhR Activation, AhR
2 KE 944 dimerization, AHR/ARNT dimerization, AHR/ARNT
3 KE 1697 Increase, DNA methyltransferase expression Increase, DNMT expression
4 KE 1698 Increase, hypermethylation of the promotor region of gonadotropin releasing hormone receptor Increase, hypermethylation of the promotor region of GnRHR
5 KE 1699 Decrease, expression of gonadotropin releasing hormone receptor Decease, expression of GnRHR
6 KE 3 Reduction, 17beta-estradiol synthesis by ovarian granulosa cells Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
7 KE 219 Reduction, Plasma 17beta-estradiol concentrations Reduction, Plasma 17beta-estradiol concentrations
8 KE 285 Reduction, Vitellogenin synthesis in liver Reduction, Vitellogenin synthesis in liver
9 KE 221 Reduction, Plasma vitellogenin concentrations Reduction, Plasma vitellogenin concentrations
10 KE 309 Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development
11 AO 78 Reduction, Cumulative fecundity and spawning Reduction, Cumulative fecundity and spawning
12 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
Activation, AhR leads to dimerization, AHR/ARNT adjacent High Moderate
dimerization, AHR/ARNT leads to Increase, DNMT expression adjacent Moderate Low
Increase, DNMT expression leads to Increase, hypermethylation of the promotor region of GnRHR adjacent Moderate Low
Increase, hypermethylation of the promotor region of GnRHR leads to Decease, expression of GnRHR adjacent Moderate Low
Decease, expression of GnRHR leads to Reduction, 17beta-estradiol synthesis by ovarian granulosa cells adjacent Moderate Low
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 Moderate
Reduction, Plasma vitellogenin concentrations leads to Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development adjacent Moderate Low
Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development leads to Reduction, Cumulative fecundity and spawning adjacent Moderate Moderate
Reduction, Cumulative fecundity and spawning leads to Decrease, Population trajectory adjacent Moderate Moderate
Reduction, Plasma 17beta-estradiol concentrations leads to Reduction, Plasma vitellogenin concentrations non-adjacent High Moderate

Network View

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Stressors

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Name Evidence Term
benzo[a]pyrene Moderate

Life Stage Applicability

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Life stage Evidence
Embryo High
Adult, reproductively mature High

Taxonomic Applicability

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Term Scientific Term Evidence Link
zebrafish Danio rerio Moderate 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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