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Inhibition of thyroid peroxidase leading to impaired fertility in fish
Point of Contact
- June-Woo Park
- Young Jun Kim
- Carlie LaLone
- Chang-Beom Park
- Dan Villeneuve
- Shihori Tanabe
|Handbook Version||OECD status||OECD project|
This AOP was last modified on June 07, 2023 05:33
Revision dates for related pages
|Thyroperoxidase, Inhibition||November 04, 2022 09:24|
|Thyroid hormone synthesis, Decreased||November 04, 2022 09:25|
|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||November 04, 2022 09:27|
|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|
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
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)
Summary of the AOP
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)
Life Stage Applicability
|Adult, reproductively mature||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).
Known Modulating Factors
|Modulating Factor (MF)||Influence or Outcome||KER(s) involved|
Considerations for Potential Applications of the AOP (optional)
The continuous release of thyroid hormones into the bloodstream is integral to properly regulating these excretory systems. The thyroid gland produces a relatively inactive prohormone, thyroxine (T4), and an active hormone called triiodothyronine (T3). The levels of THs T4 and T3 and that of the thyroid-stimulating hormone (TSH) in vivo are representative assays for identifying thyroid disturbance factors during toxicity tests. The in vivo TH levels in response to thyroid-disrupting chemicals can be measured based on the test guidelines (TGs) of the Organization for Economic Cooperation and Development (OECD). The effects of the TS microspheres on the function and fate of 3D thyroid cells can be applied to this AOP. In addition, the zebrafish embryo evaluation model is validated with the proposed TS-microsphere integrated 3D cell aggregates in terms of sensitivity to chemical substances. It can be applied to the organization of tissue and organ level as quantitative AOP271,
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