
This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Aop: 271
Title
Inhibition of thyroid peroxidase leading to impaired fertility in fish
Short name
Graphical Representation
Point of Contact
Contributors
- June-Woo Park
- Carlie LaLone
- Young Jun Kim
- Cataia Ives
Status
Author status | OECD status | OECD project | SAAOP status |
---|---|---|---|
Open for comment. Do not cite | Under Development | 1.59 | Included in OECD Work Plan |
This AOP was last modified on July 16, 2022 18:37
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Thyroperoxidase, Inhibition | July 08, 2022 06:36 |
Thyroid hormone synthesis, Decreased | July 08, 2022 06:44 |
Reduction, Plasma 17beta-estradiol concentrations | September 26, 2017 11:30 |
Reduction, Plasma vitellogenin concentrations | September 16, 2017 10:14 |
Reduction, Cumulative fecundity and spawning | March 20, 2017 17:52 |
Thyroperoxidase, Inhibition leads to TH synthesis, Decreased | July 08, 2022 07:51 |
TH synthesis, Decreased leads to Reduction, Plasma 17beta-estradiol concentrations | September 18, 2018 20:54 |
Reduction, Plasma 17beta-estradiol concentrations leads to Reduction, Plasma vitellogenin concentrations | October 18, 2018 11:02 |
Reduction, Plasma vitellogenin concentrations leads to Reduction, Cumulative fecundity and spawning | September 18, 2018 20:55 |
Propylthiouracil | November 29, 2016 18:42 |
Methimazole | November 29, 2016 18:42 |
Ethylene thiourea | November 29, 2016 18:42 |
Abstract
This AOP links inhibition of thyroid peroxidase to reproductive toxicity in fish. This AOP describes one adverse outcome that may result from the inhibition of thyroid peroxidase (TPO). Thyroid peroxidase (TPO) is an enzyme for thyroid hormone (TH) synthesis. Chemical inhibition of TPO, the molecular-initiating event (MIE), results in decreased thyroid hormone (TH) synthesis. Reduction of TH induces the decline of E2 and VTG, which leads to decreased cumulative fecundity and spawning. Cumulative fertility is major endpoint for evaluation of reproductive toxicity caused by endocrine disruption. It is used as an endpoint for endocrine disruptor screening in OECD 229. Therefore, this AOP would be useful as a means to identify chemicals with known potential to adversely affect fish populations.
AOP Development Strategy
Context
Acknowledgements: This research was supported by the National Research Council of Science & Technology(NST) grant by the Korea government (MSIP) (No. CAP-17-01-KIST Europe)
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
---|
MIE | 279 | Thyroperoxidase, Inhibition | Thyroperoxidase, Inhibition |
KE | 277 | Thyroid hormone synthesis, Decreased | TH synthesis, Decreased |
KE | 219 | Reduction, Plasma 17beta-estradiol concentrations | Reduction, Plasma 17beta-estradiol concentrations |
KE | 221 | Reduction, Plasma vitellogenin concentrations | Reduction, Plasma vitellogenin concentrations |
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
Life stage | Evidence |
---|---|
Adult, reproductively mature | High |
Taxonomic Applicability
Term | Scientific Term | Evidence | Link |
---|---|---|---|
fish | fish | High | NCBI |
Sex Applicability
Sex | Evidence |
---|---|
Female | High |
Overall Assessment of the AOP
Domain of Applicability
Essentiality of the Key Events
- MIE: Thyroperoxidase, Inhibition: The present MIE, an inhibition peroxidase (TPO) function led to a perturbation in the expression of key genes in thyroid hormone synthesis and release pathways. Specifically as the TPO inhibited by MMI and PTU was reflected in the several thyroid hormone synthesis and release pathway genes (Alison et al., 2012).
- KE 1: Thyroid hormone synthesis, Decrease: A lot of studies have a correlation between TPO activition leading to decrease of thyroid hormone. Many studies was exposed that TPO inhibition lead to a decreased or inactivate of thyroid hormones levels (Shaoying et al., 2011; Antonio et al., 2006; Tonacchera et al., 2004; De Groef et al., 2006; Waltz wt al., 2010).
Evidence Assessment
Known Modulating Factors
Quantitative Understanding
Considerations for Potential Applications of the AOP (optional)
References
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