
This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Aop: 456
Title
Aryl hydrocarbon receptor activation leading to early life stage mortality via cardiovascular toxicity
Short name
Graphical Representation
Point of Contact
Contributors
- Prarthana Shankar
Status
Author status | OECD status | OECD project | SAAOP status |
---|---|---|---|
Under development: Not open for comment. Do not cite |
This AOP was last modified on August 11, 2022 19:28
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Activation, AhR | March 22, 2018 14:00 |
dimerization, AHR/ARNT | September 16, 2017 10:14 |
Decrease, sox9 expression | August 11, 2022 15:09 |
Increase, slincR expression | August 01, 2022 13:37 |
Altered, Cardiovascular development/function | September 16, 2017 10:14 |
Increase, Early Life Stage Mortality | March 22, 2018 10:23 |
Activation, AhR leads to dimerization, AHR/ARNT | March 22, 2018 11:02 |
Activation, AhR leads to Decrease, sox9 expression | August 11, 2022 13:04 |
dimerization, AHR/ARNT leads to Increase, slincR expression | July 29, 2022 13:26 |
Increase, slincR expression leads to Altered, Cardiovascular development/function | August 02, 2022 23:21 |
Increase, slincR expression leads to Decrease, sox9 expression | August 11, 2022 14:28 |
Decrease, sox9 expression leads to Altered, Cardiovascular development/function | August 04, 2022 18:15 |
Altered, Cardiovascular development/function leads to Increase, Early Life Stage Mortality | March 23, 2018 14:29 |
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) | February 09, 2017 14:32 |
Abstract
The Aryl Hydrocarbon Receptor (Ahrs) are evolutionarily conserved ligand-dependent transcription factors that can be activated by structurally diverse compounds such as halogenated aromatic hydrocarbons, polycyclic aromatic hydrocarbons, and polychlorinated biphenyls. Ahr activation can cause developmental toxicity, including cardiovascular toxicity, that can lead to early-stage mortality. The current AOP describes a novel adverse outcome pathway (AOP) which describe how Ahr activation (molecular initiating event; MIE) can lead to early-stage mortality (adverse outcome; AO), via cardiovascular toxicity. The AOP includes two novel key events (KEs), increase in slincR expression, a newly characterized long non-coding RNA that has regulatory functions, and decrease in sox9 expression, a critical transcription factor implicated in several processes including cardiovascular development. Using a key event relationship (KER)-by-KER approach, we collected evidence using both relevant zebrafish literature as well as through broader key word searches in the AbstractSifter tool. Weight of evidence for each KER was assessed to inform overall assessment of the two AOPs which is presented here. Overall confidence levels ranged between medium and strong, with few inconsistencies as well several opportunities for future research identified. While the AOP has only been demonstrated in zebrafish with TCDD as an Ahr activator, we provide lines of evidence for the AOP to apply to majority of animals, as well as many Ahr activating chemicals. The addition of the AOP into the AOP-Wiki helps expand the growing Ahr-related AOP network.
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 |
---|
MIE | 18 | Activation, AhR | Activation, AhR |
KE | 944 | dimerization, AHR/ARNT | dimerization, AHR/ARNT |
KE | 2021 | Increase, slincR expression | Increase, slincR expression |
KE | 2020 | Decrease, sox9 expression | Decrease, sox9 expression |
KE | 317 | Altered, Cardiovascular development/function | Altered, Cardiovascular development/function |
AO | 947 | Increase, Early Life Stage Mortality | Increase, Early Life Stage Mortality |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
---|
Activation, AhR leads to dimerization, AHR/ARNT | adjacent | High | High |
dimerization, AHR/ARNT leads to Increase, slincR expression | adjacent | High | High |
Increase, slincR expression leads to Decrease, sox9 expression | adjacent | High | High |
Decrease, sox9 expression leads to Altered, Cardiovascular development/function | adjacent | High | |
Altered, Cardiovascular development/function leads to Increase, Early Life Stage Mortality | adjacent | High | High |
Activation, AhR leads to Decrease, sox9 expression | non-adjacent | High | High |
Increase, slincR expression leads to Altered, Cardiovascular development/function | non-adjacent | Moderate | Moderate |
Network View
Prototypical Stressors
Life Stage Applicability
Life stage | Evidence |
---|---|
Embryo | High |
Development | High |
Taxonomic Applicability
Sex Applicability
Sex | Evidence |
---|---|
Unspecific | High |