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AOP: 496
Title
Androgen receptor agonism leading to reproduction dysfunction (in zebrafish)
Short name
Graphical Representation
Point of Contact
Contributors
- Hongling Liu
Coaches
OECD Information Table
OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
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This AOP was last modified on November 16, 2024 04:49
Revision dates for related pages
Page | Revision Date/Time |
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Agonism, Androgen receptor | November 05, 2024 07:49 |
Increase, Gonadotropins concentration in plasma | May 16, 2023 21:50 |
Reduction, Plasma 17beta-estradiol concentrations | September 26, 2017 11:30 |
Reduction, the ratio of 17beta-estradiol/11-Keto Testosterone in plasma | May 16, 2023 22:04 |
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 |
Decreased, Population trajectory | April 18, 2017 16:19 |
Decrease, circulating testosterone levels | January 27, 2025 03:37 |
Altered, Transcription of genes by the androgen receptor | April 05, 2024 09:28 |
Agonism, Androgen receptor leads to Altered, Transcription of genes by the AR | November 16, 2024 04:36 |
Reduction, Plasma 17beta-estradiol concentrations leads to Reduction, Plasma vitellogenin concentrations | October 18, 2018 11:02 |
Reduction, the ratio of E2/11-KT in plasma leads to Increase, Gonadotropins concentration in plasma | November 16, 2024 04:41 |
Decrease, circulating testosterone levels leads to Reduction, Plasma 17beta-estradiol concentrations | May 08, 2024 21:09 |
Reduction, Plasma 17beta-estradiol concentrations leads to Reduction, the ratio of E2/11-KT in plasma | May 22, 2023 21:39 |
Reduction, the ratio of E2/11-KT in plasma leads to Reduction, Plasma vitellogenin concentrations | May 22, 2023 21:40 |
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 Decreased, Population trajectory | May 22, 2023 21:44 |
Decrease, circulating testosterone levels leads to Reduction, the ratio of E2/11-KT in plasma | May 08, 2024 21:11 |
17beta-Trenbolone | November 29, 2016 18:42 |
Abstract
This adverse outcome pathway is a further development and improvement for AOP 23 and details the linkage of androgen receptor agonism in female zebrafish with reproductive dysfunction and reductions of cumulative fecundity and spawning as adverse effect. Based on AOP 23, it also adds some new KEs for the pathway and quantitative understanding for key events through experiments data. This work found that there are some differences and similarities in KEs between zebrafish and Pimephales promelas induced by androgen receptor agonism. The impairments in zebrafish in vivo is connected with androgen receptor activities in vitro by agonism.
The 21-day exposure experiments to adult zebrafish revealed that female zebrafish showed strong dose-response relationships to the androgen receptor agonism (17beta-trenbolone) at the genetic, enzymatic, tissue, and individual levels than male zebrafish. The quantitative relationships from experiments and evidence analysis revealed stronger evidence of androgen agonism, ar gene expression, circulating E2 and VTG concentrations in plasma, and spawning, while weaker evidence and dose-effect results in GtH and T concentrations in plasma, and oocytes development. In addition, it was the ratio of E2/11-KT rather than E2/T that became an important KE to reveal the transformation of T to E2 when qualitative and quantitative relationship were considered, since T will be catalyzed by aromatase (CYP19A1A and CYP11C1) and transform into E2 or 11-KT.
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 |
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MIE | 25 | Agonism, Androgen receptor | Agonism, Androgen receptor |
KE | 286 | Altered, Transcription of genes by the androgen receptor | Altered, Transcription of genes by the AR |
KE | 2137 | Increase, Gonadotropins concentration in plasma | Increase, Gonadotropins concentration in plasma |
KE | 1690 | Decrease, circulating testosterone levels | Decrease, circulating testosterone levels |
KE | 219 | Reduction, Plasma 17beta-estradiol concentrations | Reduction, Plasma 17beta-estradiol concentrations |
KE | 2139 | Reduction, the ratio of 17beta-estradiol/11-Keto Testosterone in plasma | Reduction, the ratio of E2/11-KT in plasma |
KE | 221 | Reduction, Plasma vitellogenin concentrations | Reduction, Plasma vitellogenin concentrations |
KE | 309 | Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development | Reduction, Vitellogenin accumulation into oocytes and oocyte growth/development |
KE | 78 | Reduction, Cumulative fecundity and spawning | Reduction, Cumulative fecundity and spawning |
AO | 442 | Decreased, Population trajectory | Decreased, Population trajectory |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
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Network View
Prototypical Stressors
Name |
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17beta-Trenbolone |
Life Stage Applicability
Life stage | Evidence |
---|---|
Adult, reproductively mature | High |
Taxonomic Applicability
Term | Scientific Term | Evidence | Link |
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zebrafish | Danio rerio | High | NCBI |
Sex Applicability
Sex | Evidence |
---|---|
Female | 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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