This AOP is licensed under the BY-SA license. This license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. If you remix, adapt, or build upon the material, you must license the modified material under identical terms.
AOP: 537
Title
Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver
Short name
Graphical Representation
Point of Contact
Contributors
- Jason M. O'Brien
Coaches
OECD Information Table
OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
---|---|---|---|---|
This AOP was last modified on July 09, 2024 14:54
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Agonism, Estrogen receptor | June 24, 2024 13:35 |
Increase, Vitellogenin synthesis in liver | June 24, 2024 13:38 |
Increase, Plasma vitellogenin concentrations | June 24, 2024 13:39 |
Impaired development of, Reproductive organs | December 03, 2016 16:33 |
Reduction, Cumulative fecundity and spawning | March 20, 2017 17:52 |
Agonism, Estrogen receptor leads to Increase, Vitellogenin synthesis in liver | June 24, 2024 13:04 |
Increase, Vitellogenin synthesis in liver leads to Increase, Plasma vitellogenin concentrations | June 24, 2024 13:13 |
Increase, Plasma vitellogenin concentrations leads to Impaired development of, Reproductive organs | July 03, 2024 13:57 |
Impaired development of, Reproductive organs leads to Reduction, Cumulative fecundity and spawning | July 03, 2024 13:57 |
Abstract
This adverse outcome pathway describes a series of key events starting from agonism of the estrogen receptor (ESR) leading to reduced fecundity. It was originally developed to support applications in avian models (cell culture and egg injection studies) but is likely relevant to all oviparous species. In fact, all of the KEs are borrowed from fish-related AOPs. The series of events in this AOP are ESR agonism, increased vitellogenin in the liver, then increased vitellogenin in plasma, followed by impaired reproductive organ development and ultimately leading to impaired reproduction (reduced fecundity). This AOP will have utility in screening chemicals for estrogenic activity.
AOP Development Strategy
Context
Strategy
2024-07-02: Originally developed as a putative AOP to support applications in avian cell culture and egg injection studies. It was built from existing KEs from fish-related AOPs. The KE and KERs were supplemented with very limited data avian-specific data. There are no current plans to develop this AOP to a level where it can be submitted for review. Therefore, others are encouraged to contribute to this AOP.
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
---|
MIE | 111 | Agonism, Estrogen receptor | Agonism, Estrogen receptor |
KE | 307 | Increase, Vitellogenin synthesis in liver | Increase, Vitellogenin synthesis in liver |
KE | 220 | Increase, Plasma vitellogenin concentrations | Increase, Plasma vitellogenin concentrations |
KE | 364 | Impaired development of, Reproductive organs | Impaired development of, Reproductive organs |
AO | 78 | Reduction, Cumulative fecundity and spawning | Reduction, Cumulative fecundity and spawning |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
---|
Network View
Prototypical Stressors
Life Stage Applicability
Taxonomic Applicability
Sex Applicability
Overall Assessment of the AOP
Domain of Applicability
- Sex: The AOP currently only describes evidence for the later KEs and KERs in males, though they are believed to be relevant to both sexes.
- Life stage: The AO is most relevant during embryonic development when the reproductive organs are forming, although the upstream KEs can be measured at other life stages.
- Taxonomic: This AOP has supporting evidence from avian and fish experiments, though it is likely relevant to all oviparous species.
Essentiality of the Key Events
Evidence Assessment
Known Modulating Factors
Modulating Factor (MF) | Influence or Outcome | KER(s) involved |
---|---|---|