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Relationship: 2213


A descriptive phrase which clearly defines the two KEs being considered and the sequential relationship between them (i.e., which is upstream, and which is downstream). More help

Reduced, Posterior swim bladder inflation leads to Increased Mortality

Upstream event
The causing Key Event (KE) in a Key Event Relationship (KER). More help
Downstream event
The responding Key Event (KE) in a Key Event Relationship (KER). More help

Key Event Relationship Overview

The utility of AOPs for regulatory application is defined, to a large extent, by the confidence and precision with which they facilitate extrapolation of data measured at low levels of biological organisation to predicted outcomes at higher levels of organisation and the extent to which they can link biological effect measurements to their specific causes.Within the AOP framework, the predictive relationships that facilitate extrapolation are represented by the KERs. Consequently, the overall WoE for an AOP is a reflection in part, of the level of confidence in the underlying series of KERs it encompasses. Therefore, describing the KERs in an AOP involves assembling and organising the types of information and evidence that defines the scientific basis for inferring the probable change in, or state of, a downstream KE from the known or measured state of an upstream KE. More help

AOPs Referencing Relationship

AOP Name Adjacency Weight of Evidence Quantitative Understanding Point of Contact Author Status OECD Status
Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation non-adjacent High Low Brendan Ferreri-Hanberry (send email) Under Development: Contributions and Comments Welcome WPHA/WNT Endorsed
Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation non-adjacent High Low Agnes Aggy (send email) Under Development: Contributions and Comments Welcome WPHA/WNT Endorsed

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KER.In general, this will be dictated by the more restrictive of the two KEs being linked together by the KER.  More help
Term Scientific Term Evidence Link
zebrafish Danio rerio High NCBI
fathead minnow Pimephales promelas Moderate NCBI

Sex Applicability

An indication of the the relevant sex for this KER. More help
Sex Evidence
Unspecific Moderate

Life Stage Applicability

An indication of the the relevant life stage(s) for this KER.  More help
Term Evidence
Embryo High
Larvae High

Key Event Relationship Description

Provides a concise overview of the information given below as well as addressing details that aren’t inherent in the description of the KEs themselves. More help

Because of its roles in energy sparing and swimming performance, it is expected that failure to inflate the swim bladder would create increased oxygen and energy demands leading to decreased growth, which in turn leads to decreased probability of survival.

Evidence Collection Strategy

Include a description of the approach for identification and assembly of the evidence base for the KER. For evidence identification, include, for example, a description of the sources and dates of information consulted including expert knowledge, databases searched and associated search terms/strings.  Include also a description of study screening criteria and methodology, study quality assessment considerations, the data extraction strategy and links to any repositories/databases of relevant references.Tabular summaries and links to relevant supporting documentation are encouraged, wherever possible. More help

Evidence Supporting this KER

Addresses the scientific evidence supporting KERs in an AOP setting the stage for overall assessment of the AOP. More help

There is strong evidence for a link between reduced posterior chamber inflation and increased mortality across different fish species. 

Biological Plausibility
Addresses the biological rationale for a connection between KEupstream and KEdownstream.  This field can also incorporate additional mechanistic details that help inform the relationship between KEs, this is useful when it is not practical/pragmatic to represent these details as separate KEs due to the difficulty or relative infrequency with which it is likely to be measured.   More help

The posterior chamber of the swim bladder has a function in regulating the buoyancy of fish (Roberston et al., 2007). Fish rely on the lipid and gas content in their body to regulate their position within the water column. Efficient regulation of buoyancy is energy sparing and allows for fish to expend less energy in maintaining and changing positions in the water column. Because of its roles in energy sparing and swimming performance, it is expected that failure to inflate the swim bladder would create increased oxygen and energy demands leading to decreased growth, which in turn leads to decreased probability of survival. In particular, these impacts would be expected in non-laboratory environments where fish must expend energy to capture food and avoid predators and where available food is limited. Additionally, fish without a functional swim bladder are severely disadvantaged in terms of foraging and avoiding predators, making the likelihood of surviving smaller.

Uncertainties and Inconsistencies
Addresses inconsistencies or uncertainties in the relationship including the identification of experimental details that may explain apparent deviations from the expected patterns of concordance. More help

Some studies showed an absence of increased mortality after impaied posterior chamber inflation but this is probably caused by the fact that observation was limited to short term effects (e.g., Wang et al., 2020). Observations of absence of mortality often performed at 96/120 hpf in zebrafish, which is immediately after posterior chamber inflation.

Known modulating factors

This table captures specific information on the MF, its properties, how it affects the KER and respective references.1.) What is the modulating factor? Name the factor for which solid evidence exists that it influences this KER. Examples: age, sex, genotype, diet 2.) Details of this modulating factor. Specify which features of this MF are relevant for this KER. Examples: a specific age range or a specific biological age (defined by...); a specific gene mutation or variant, a specific nutrient (deficit or surplus); a sex-specific homone; a certain threshold value (e.g. serum levels of a chemical above...) 3.) Description of how this modulating factor affects this KER. Describe the provable modification of the KER (also quantitatively, if known). Examples: increase or decrease of the magnitude of effect (by a factor of...); change of the time-course of the effect (onset delay by...); alteration of the probability of the effect; increase or decrease of the sensitivity of the downstream effect (by a factor of...) 4.) Provision of supporting scientific evidence for an effect of this MF on this KER. Give a list of references.  More help
Response-response Relationship
Provides sources of data that define the response-response relationships between the KEs.  More help
Information regarding the approximate time-scale of the changes in KEdownstream relative to changes in KEupstream (i.e., do effects on KEdownstream lag those on KEupstream by seconds, minutes, hours, or days?). More help
Known Feedforward/Feedback loops influencing this KER
Define whether there are known positive or negative feedback mechanisms involved and what is understood about their time-course and homeostatic limits. More help

Domain of Applicability

A free-text section of the KER description that the developers can use to explain their rationale for the taxonomic, life stage, or sex applicability structured terms. More help

Taxonomic: The literature provides strong support for the relevance of this KER for physoclistous fish (e.g., yellow perch, Japanese Medaka) whose inflation occurs at a critical time in development when the fish must gulp air to inflate its swim bladder before the pneumatic duct closes. The relevance to physostomes (such as zebrafish and fathead minnows) that maintain an open pneumatic duct into adulthood is less apparent. The latter likely have greater potential to inflate the swim bladder at some point in development, even if early larval inflation is impaired. However, it is plausible that structural damage that prevented inflation of the organ in a phystostome would be expected to cause similar effects.

Life stage: This KER is applicable to early embry-larval development, which is the period where the posterior swim bladder chamber inflates and larvae start to freely feed. To what extent fish can survive with partly inflated swim bladders during later life stages is unknown.

Sex: This KER is probably not sex-dependent since both females and males rely on the posterior swim bladder chamber to regulate buyoancy. Furthermore, 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 posterior chamber inflates around 5 days post fertilization, when sex differentiation has not started yet, sex differences are expected to play a minor role.


List of the literature that was cited for this KER description. More help

Brown, C. L., Doroshov, S. I., Nunez, J. M., Hadley, C., Vaneenennaam, J., Nishioka, R. S. and Bern, H. A. (1988), Maternal triiodothyronine injections cause increases in swimbladder inflation and survival rates in larval striped bass, Morone saxatilis. J. Exp. Zool., 248: 168–176. doi: 10.1002/jez.1402480207

Chatain B (1994) Abnormal swimbladder development and lordosis in sea bass (Dicentrarcus-labrax) ans sea bream (Sparus-auratus). Aquaculture 119 (4): 371-9

Chatain, Beatrice. "Problems related to the lack of functional swimbladder in intensive rearing of the seabass Dicentrarchus labrax and the sea bream Sparus auratus." Advances in Tropical Aquaculture, Workshop at Tahiti, French Polynesia, 20 Feb-4 Mar 1989. 1989.

Dong W, Liu J, Wei LX, Yang JF, Chernick M, Hinton DE. 2016. Developmental toxicity from exposure to various forms of mercury compounds in medaka fish (oryzias latipes) embryos. Peerj. 4.

Egloff, M. 1996. Failure of swim bladder inflation of perch, Perca fluviatilis, L. found in natural populations. Aquat. Sci. 58(1):15-23.

Gary D. Marty , David E. Hinton & Joseph J. Cech Jr. (1995) Notes: Oxygen Consumption by Larval Japanese Medaka with Inflated or Uninflated Swim Bladders, Transactions of the American Fisheries Society, 124:4, 623-627, DOI: 10.1577/1548-8659(1995).

Goolish, E. M. and Okutake, K. (1999), Lack of gas bladder inflation by the larvae of zebrafish in the absence of an air-water interface. Journal of Fish Biology, 55: 1054–1063. doi:10.1111/j.1095-8649.1999.tb00740.x

Greg A. Kindschi & Frederic T. Barrows (1993) Survey of Swim Bladder Inflation in Walleyes Reared in Hatchery Production Ponds, The Progressive Fish-Culturist, 55:4,219-223, DOI: 10.1577/1548-8640(1993)055<0219:SOSBII>2.3.CO;2

Horie Y, Chiba T, Takahashi C, Tatarazako N, Iguchi T. 2021. Influence of triphenyltin on morphologic abnormalities and the thyroid hormone system in early-stage zebrafish (danio rerio). Comparative Biochemistry and Physiology C-Toxicology & Pharmacology. 242.

Kindschi GA, Barrows FT (1993) Survey of swim bladder inflation in walleyes reared in hatchery production ponds. Progressive Fish-Culturist 55 (4): 219-23

Martin-Robichaud, D. J. and Peterson, R. H. (1998), Effects of light intensity, tank colour and photoperiod on swimbladder inflation success in larval striped bass, Morone saxatilis (Walbaum). Aquaculture Research, 29: 539–547. doi: 10.1046/j.1365-2109.1998.00234.

Mu JL, Chernick M, Dong W, Di Giulio RT, Hinton DE. 2017. Early life co-exposures to a real-world pah mixture and hypoxia result in later life and next generation consequences in medaka (oryzias latipes). Aquatic Toxicology. 190:162-173.

Sergiusz J. Czesny, Brian D. S. Graeb & John M. Dettmers (2005): Ecological Consequences of Swim Bladder Noninflation for Larval Yellow Perch, Transactions of the American Fisheries Society, 134:4, 1011-1020.

Stinckens, E., Vergauwen, L., Blackwell, B.R., Anldey, G.T., Villeneuve, D.L., Knapen, D., 2020. Effect of Thyroperoxidase and Deiodinase Inhibition on Anterior Swim Bladder Inflation in the Zebrafish. Environmental Science & Technology 54, 6213-6223.

Wang JX, Shi GH, Yao JZ, Sheng N, Cui RN, Su ZB, Guo Y, Dai JY. 2020. Perfluoropolyether carboxylic acids (novel alternatives to pfoa) impair zebrafish posterior swim bladder development via thyroid hormone disruption. Environment International. 134.

Woolley, L. D. and Qin, J. G. (2010), Swimbladder inflation and its implication to the culture of marine finfish larvae. Reviews in Aquaculture, 2: 181–190. doi: 10.1111/j.1753-5131.2010.01035.x