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Aop: 157

AOP Title

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Deiodinase 1 inhibition leading to reduced young of year survival via posterior swim bladder inflation

Short name:

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DIO1i posterior swim bladder

Graphical Representation

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Click to download graphical representation template

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Authors

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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

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Dries Knapen   (email point of contact)

Contributors

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  • Dries Knapen
  • Lucia Vergauwen

Status

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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 Do not cite Under Development 1.35 Included in OECD Work Plan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 March 01, 2019 09:36

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Revision dates for related pages

Page Revision Date/Time
Inhibition, Deiodinase 1 November 29, 2016 19:36
Decrease, Population trajectory September 26, 2017 11:33
Decreased, Triiodothyronine (T3) in serum September 26, 2017 11:03
Reduced, Posterior swim bladder inflation February 18, 2019 10:52
Reduced, Swimming performance November 29, 2016 19:36
Reduced, Young of year survival November 29, 2016 19:36
Reduced, Anterior swim bladder inflation February 18, 2019 10:51
Reduced, Hearing February 18, 2019 10:50
Inhibition, Deiodinase 1 leads to Decreased, Triiodothyronine (T3) in serum March 15, 2019 06:18
Decreased, Triiodothyronine (T3) in serum leads to Reduced, Posterior swim bladder inflation March 08, 2019 11:22
Reduced, Posterior swim bladder inflation leads to Reduced, Swimming performance November 29, 2016 20:51
Reduced, Swimming performance leads to Reduced, Young of year survival December 03, 2016 16:38
Reduced, Young of year survival leads to Decrease, Population trajectory December 03, 2016 16:38
Reduced, Posterior swim bladder inflation leads to Reduced, Anterior swim bladder inflation March 08, 2019 08:43
Reduced, Anterior swim bladder inflation leads to Reduced, Hearing December 03, 2016 16:38
Reduced, Hearing leads to Reduced, Young of year survival December 03, 2016 16:38
Reduced, Anterior swim bladder inflation leads to Reduced, Swimming performance November 29, 2016 20:52
Inhibition, Deiodinase 1 leads to Reduced, Posterior swim bladder inflation March 15, 2019 06:16
Reduced, Posterior swim bladder inflation leads to Reduced, Young of year survival March 08, 2019 08:33
Propylthiouracil November 29, 2016 18:42

Abstract

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The AOP describes the effects of inhibition of iodothyronine deiodinase 1 (DIO1) on posterior swim bladder inflation in fish leading to reduced young of year survival and population trajectory decline. DIO1 and DIO2 are thryoid hormone (TH) activating deiodinases that convert thyroxin (T4) to the more biologically active 3,5,3′-triiodothyronine (T3). The inhibition of DIO1 results in decreased circulating concentrations of T3 in serum. Disruption of the TH system is increasingly being recognized as an important mode of action 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. Chemicals interfering with the conversion of T4 to T3 by inhibiting DIO1 have the potential to inhibit posterior chamber inflation which may result in 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. The current state of the art suggests that DIO2 is more important than DIO1 in regulating posterior chamber inflation. Therefore the corresponding AOP leading from DIO2 inhibition to reduced young of year survival via posterior swim bladder inflation may be of higher biological relevance compared to the AOP that is described here.


Background (optional)

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Summary of the AOP

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Events: Molecular Initiating Events (MIE)

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Key Events (KE)

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Adverse Outcomes (AO)

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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 1004 Reduced, Posterior swim bladder inflation Reduced, Posterior swim bladder inflation
4 KE 1005 Reduced, Swimming performance Reduced, Swimming performance
5 KE 1006 Reduced, Young of year survival Reduced, Young of year survival
6 KE 1007 Reduced, Anterior swim bladder inflation Reduced, Anterior swim bladder inflation
7 KE 1008 Reduced, Hearing Reduced, Hearing
8 AO 360 Decrease, Population trajectory Decrease, Population trajectory

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Inhibition, Deiodinase 1 leads to Decreased, Triiodothyronine (T3) in serum adjacent
Decreased, Triiodothyronine (T3) in serum leads to Reduced, Posterior swim bladder inflation adjacent Moderate Low
Reduced, Posterior swim bladder inflation leads to Reduced, Swimming performance adjacent
Reduced, Swimming performance leads to Reduced, Young of year survival adjacent
Reduced, Young of year survival leads to Decrease, Population trajectory adjacent
Reduced, Posterior swim bladder inflation leads to Reduced, Anterior swim bladder inflation adjacent
Reduced, Anterior swim bladder inflation leads to Reduced, Hearing adjacent
Reduced, Hearing leads to Reduced, Young of year survival adjacent
Reduced, Anterior swim bladder inflation leads to Reduced, Swimming performance adjacent
Inhibition, Deiodinase 1 leads to Reduced, Posterior swim bladder inflation non-adjacent Moderate Low
Reduced, Posterior swim bladder inflation leads to Reduced, Young of year survival non-adjacent High Low

Network View

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Stressors

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Name Evidence Term
Propylthiouracil

Life Stage Applicability

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Life stage Evidence
Embryo High

Taxonomic Applicability

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Term Scientific Term Evidence Link
zebrafish Danio rerio NCBI
fathead minnow Pimephales promelas NCBI

Sex Applicability

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Sex Evidence
Unspecific

Overall Assessment of the AOP

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Domain of Applicability

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Essentiality of the Key Events

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Evidence Assessment

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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

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