Aop: 158
AOP Title
Short name:
DIO1i anterior swim bladderGraphical Representation
Click to download graphical representation template
Authors
Dries Knapen [1], [dries.knapen (at)uantwerpen.be]
Lucia Vergauwen [1], [lucia.vergauwen(at)uantwerpen.be]
Evelyn Stinckens [1], [evelyn.stinckens(at)uantwerpen.be]
Dan Villeneuve [2], [villeneuve.dan*(at)epa.gov]
[1] Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium
[2] United States Environmental Protection Agency, Mid-Continent Ecology Division, 6201 Congdon Blvd, Duluth, MN, USA.
Point of Contact
Dries Knapen (email point of contact)
Contributors
- Dries Knapen
- Lucia Vergauwen
Status
| Author status | OECD status | OECD project | SAAOP status |
|---|---|---|---|
| Under development: Not open for comment. Do not cite | Under Development | 1.35 | Included in OECD Work Plan |
This AOP was last modified on June 09, 2020 12:20
Revision dates for related pages
| Page | Revision Date/Time |
|---|---|
| Inhibition, Deiodinase 1 | September 18, 2019 07:58 |
| Decrease, Population trajectory | September 26, 2017 11:33 |
| Decreased, Triiodothyronine (T3) in serum | September 26, 2017 11:03 |
| Reduced, Anterior swim bladder inflation | August 26, 2020 11:53 |
| Reduced, Swimming performance | April 24, 2020 15:05 |
| Reduced, Young of year survival | November 29, 2016 19:36 |
| Inhibition, Deiodinase 1 leads to Decreased, Triiodothyronine (T3) in serum | August 26, 2020 07:41 |
| Decreased, Triiodothyronine (T3) in serum leads to Reduced, Anterior swim bladder inflation | August 28, 2020 04:13 |
| Reduced, Anterior swim bladder inflation leads to Reduced, Swimming performance | August 28, 2020 05:04 |
| Reduced, Swimming performance leads to Reduced, Young of year survival | August 28, 2020 05:11 |
| Reduced, Young of year survival leads to Decrease, Population trajectory | August 25, 2020 06:21 |
| Propylthiouracil | November 29, 2016 18:42 |
Abstract
The AOP describes the effects of inhibition of deiodinase 1 (DIO1) on anterior swim bladder inflation leading to reduced young of year survival and population trajectory decline. The inhibition of DIO1 is the molecular-initiating event (MIE), which results in decreased circulating concentrations of triiodothyronine (T3) in serum. Disruption of the thyroid hormone (TH) system is increasingly being recognized as an important MoA that can lead to adverse outcomes, especially during embryonic development. In fish, many different adverse effects during early development resulting from disruption of the TH endocrine system have been reported (e.g., effects on body and eye size, head-to-trunk angle, heartbeat, otolith formation, pigmentation index, swim bladder inflation, hatching time, somite formation, escape response and photoreceptor development). As in amphibians, the transition in fish between the different developmental phases, including maturation and inflation of the swim bladder, have been shown to be mediated by THs. Fish larvae exposed to PTU, a known DIO1 inhibitor, has been known to result in impairment of swim bladder inflation. Chemicals interfering with the conversion of T4 to T3 have the potential to inhibit anterior chamber inflation which may result in reduced auditory capacity and reduced swimming capacity of the fish, a relevant adverse outcome that can affect feeding behaviour and predator avoidance, resulting in lower survival probability and ultimately population trajectory decline (Czesny et al., 2005; Woolley and Qin, 2010).
Background (optional)
Summary of the AOP
Events: Molecular Initiating Events (MIE)
Key Events (KE) Adverse Outcomes (AO)| Sequence | Type | Event ID | Title | Short name |
|---|
| 1 | MIE | 1009 | Inhibition, Deiodinase 1 | Inhibition, Deiodinase 1 |
| 2 | KE | 1003 | Decreased, Triiodothyronine (T3) in serum | Decreased, Triiodothyronine (T3) in serum |
| 3 | KE | 1007 | Reduced, Anterior swim bladder inflation | Reduced, Anterior swim bladder inflation |
| 5 | KE | 1005 | Reduced, Swimming performance | Reduced, Swimming performance |
| 6 | KE | 1006 | Reduced, Young of year survival | Reduced, Young of year survival |
| 7 | AO | 360 | Decrease, Population trajectory | Decrease, Population trajectory |
Relationships Between Two Key Events
(Including MIEs and AOs)
| Title | Adjacency | Evidence | Quantitative Understanding |
|---|
Network View
Stressors
| Name | Evidence Term |
|---|---|
| Propylthiouracil |
Life Stage Applicability
| Life stage | Evidence |
|---|---|
| Development |
Taxonomic Applicability
| Term | Scientific Term | Evidence | Link |
|---|---|---|---|
| zebrafish | Danio rerio | NCBI | |
| fathead minnow | Pimephales promelas | NCBI |
Sex Applicability
| Sex | Evidence |
|---|---|
| Unspecific |
Overall Assessment of the AOP
Overall, the weight of evidence for the sequence of key events laid out in the AOP is moderate to high. Nonetheless, the exact underlying mechanism of TH disruption leading to impaired swim bladder inflation is not understood. The current domain of applicability is larval life stages of zebrafish and fathead minnow pending future research in other fish species such as medaka.
Domain of Applicability
The current AOP is only applicable to larval development, which is the period where the anterior swim bladder chamber inflates.
Sex differences are typically not investigated in tests using early life stages of fish and it is currently unclear whether sex-related differences are important in this AOP. Zebrafish are undifferentiated gonochorists since both sexes initially develop an immature ovary (Maack and Segner, 2003). Immature ovary development progresses until approximately the onset of the third week. Later, in female fish immature ovaries continue to develop further, while male fish undergo transformation of ovaries into testes. Final transformation into testes varies among male individuals, however finishes usually around 6 weeks post fertilization. Since the anterior chamber inflates around 20 days post fertilization, when sex differentiation is still in its early stages, sex differences are expected to play a minor role in the current AOP.
Essentiality of the Key Events
Overall, the confidence in the supporting data for essentiality of KEs within the AOP is high since there is direct evidence from specifically designed experimental studies (knockdown and knockout studies) illustrating that the impact on downstream KEs corresponds to what is predicted by the AOP.
Evidence Assessment
Overall, the weight of evidence for the biological plausibility of the KERs in the AOP is moderate since there is empirical support for an association between the sets of KEs and the KERs are plausible based on analogy to accepted biological relationships, but scientific understanding is not completely established. Especially for some of the upstream KERs biological plausibility is high.
Overall, the empirical support for the KERs in the AOP is moderate since dependent changes in sets of KEs following exposure to a small number of specific stressors has been demonstrated, but there are still some data gaps.
Quantitative Understanding
There is some level of quantitative understanding that can form the basis for development of a quantitative AOP. Quantitative relationships between reduced T4 and reduced T3, and between reduced T3 and reduced anterior chamber inflation were established. The latter is particularly critical for linking impaired swim bladder inflation to TH disruption.
Considerations for Potential Applications of the AOP (optional)
References
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