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Event: 1004

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Reduced, Posterior swim bladder inflation

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Reduced, Posterior swim bladder inflation
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Biological Context

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Level of Biological Organization

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Organ term
swim bladder

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
swim bladder inflation posterior chamber swim bladder decreased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE. Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
DIO2i posterior swim bladder KeyEvent Dries Knapen (send email) Under Development: Contributions and Comments Welcome WPHA/WNT Endorsed
DIO1i posterior swim bladder KeyEvent Dries Knapen (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 KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
zebrafish Danio rerio High NCBI
fathead minnow Pimephales promelas High NCBI
medaka Oryzias latipes Moderate NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
Embryo High

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Unspecific Moderate

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

The teleost swim bladder is a gas-filled structure that consists of two chambers, the posterior and anterior chamber. In zebrafish, the posterior chamber inflates around 96-120 h post fertilization (hpf) which is 2-3 days post hatch, and the anterior chamber inflates around 21 dpf (days post fertilization). In fathead minnow, the posterior and anterior chamber inflate around 6 and 14 dpf respectively.

The posterior chamber is formed from a bud originating from the foregut endoderm (Winata et al., 2009). The posterior chamber operates as a hydrostatic organ. The volume of gas in the adult swim bladder is continuously adjusted to regulate body density and buoyancy.

Many amphibians and frogs go through an embryo-larval transition phase marking the switch from endogenous feeding (from the yolk) to exogenous feeding. In zebrafish, embryonic-to-larval transition takes place around 96 hours post fertilization (hpf). As in amphibians, the transition between the different developmental phases includes maturation and inflation of the swim bladder (Liu and Chan, 2002).

Reduced inflation of the posterior chamber may manifest itself as either a complete failure to inflate the chamber or a reduced size of the chamber.

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

In several fish species, inflation of the posterior chamber can easily be observed using a stereomicroscope because the larvae are still transparent during those early developmental stages. This is for example true for zebrafish and fathead minnow. Posterior chamber size can then be measured based on photographs with a calibrator.

When observing effects on swim bladder inflation, it is important to verify that reduced swim bladder inflation occurs at concentrations significantly lower than those causing mortality, since a wide variety of chemicals cause impaired posterior chamber inflation at exposure concentrations that also cause mortality (Stinckens et al., 2018).

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Taxonomic: Teleost fish can be divided in two groups according to swim bladder morphology: physoclistous (e.g., yellow perch, sea bass, striped bass, medaka) and physostomous (e.g., zebrafish and fathead minnow). Physostomous fish retain a duct between the digestive tract and the swim bladder during adulthood allowing them to gulp air at the surface to fill the swim bladder. In contrast, in physoclistous fish, once initial inflation by gulping atmospheric air at the water surface has occurred, the swim bladder is closed off from the digestive tract and swim bladder volume is regulated by gas secretion into the swim bladder (Wooley and Qin, 2010).

Much of the evidence for impaired posterior chamber of the swim bladder currently comes from work on zebrafish and fathead minnow (Stinckens et al., 2018; Cavallin et al., 2017; Wang et al., 2020). Increasing evidence is becoming available on defects of swim bladder inflation in medaka (Oryzias latipes), a species with only one swim bladder chamber (Gonzalez-Doncel et al., 2003; Dong et al., 2016; Kupsco et al., 2016; Mu et al., 2017; Pandelides et al., 2021). Exposure to T3, methimazole, heptafluorobutanoic acid (PFBA) and tris[1,3-dichloro-2-propyl] phosphate (TDCPP) inhibited inflation of the swim bladder in female medaka. Interestingly, for those females that developed a swim bladder, exposure to methimazole and all halogenated chemicals with the exception of PFBA, resulted in larger swim bladders (Godfrey et al., 2019). Horie et al. (2022) elucidated the timing of swim bladder inflation in medaka and compared effects on the swim bladder after exposure of zebrafish and medaka to PFBA and TDCPP. This KE is plausibly applicable across fish species with swim bladders, both physostomous and physoclistous.

Life stage: The posterior chamber inflates during a specific developmental time frame. In zebrafish, the posterior chamber inflates around 96-120 hpf which is 2-3 dph. In the fathead minnow, the posterior chamber inflates around 6 dpf. In medaka, the swim bladder inflates around 2 hours post hatch (hatching occurs around 8 dpf) (Horie et al., 2022). Therefore this KE is only applicable to the embryonic life stage.

Sex: This KE is plausibly applicable to both sexes. Sex differences are not often investigated in tests using early life stages of fish. In medaka, sex can be morphologically distinguished as soon as 10 days post fertilization. Females appear more susceptible to thyroid‐induced swim bladder dysfunction compared with males (Godfrey et al., 2019). In zebrafish and fathead minnow, it is currently unclear whether sex-related differences are important in determining the magnitude of the changes in this KE. 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 in zebrafish, when sex differentiation has not started yet, sex differences are expected to play a minor role. Fathead minnow gonad differentiation also occurs during larval development. Fathead minnows utilize a XY sex determination strategy and markers can be used to genotype sex in life stages where the sex is not yet clearly defined morphologically (Olmstead et al., 2011). Ovarian differentiation starts at 10 dph followed by rapid development (Van Aerle et al., 2004). At 25 dph germ cells of all stages up to the primary oocytes stage were present and at 120 dph, vitellogenic oocytes were present. The germ cells (spermatogonia) of the developing testes only entered meiosis around 90–120 dph. Mature testes with spermatozoa are present around 150 dph. Since the posterior chamber inflates around 6 days post fertilization (1 dph) in fathead minnows, sex differences are expected to play a minor role in the current KE.


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

Cavallin, J.E., Ankley, G.T., Blackwell, B.R., Blanksma, C.A., Fay, K.A., Jensen, K.M., Kahl, M.D., Knapen, D., Kosian, P.A., Poole, S.T., Randolph, E.C., Schroeder, A.L., Vergauwen, L., Villeneuve, D.L., 2017. Impaired swim bladder inflation in early life stage fathead minnows exposed to a deiodinase inhibitor, iopanoic acid. Environmental Toxicology and Chemistry 36, 2942-2952.

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.

Godfrey A, Hooser B, Abdelmoneim A, Sepulveda MS. 2019. Sex-specific endocrine-disrupting effects of three halogenated chemicals in japanese medaka. Journal of Applied Toxicology. 39(8):1215-1223.

Gonzalez-Doncel M, de la Pena E, Barrueco C, Hinton DE. 2003. Stage sensitivity of medaka (oryzias latipes) eggs and embryos to permethrin. Aquatic Toxicology. 62(3):255-268.

Horie, Y., Nomura, M., Okamoto, K., Takahashi, C., Sato, T., Miyagawa, S., Okamura, H., Iguchi, T., 2022. Effect of thyroid hormone-disrupting chemicals on swim bladder inflation and thyroid hormone-related gene expression in Japanese medaka and zebrafish. Journal of Applied Toxicology. DOI: 10.1002/jat.4302.

Kupsco A, Schlenk D. 2016. Stage susceptibility of japanese medaka (oryzias latipes) to selenomethionine and hypersaline developmental toxicity. Environmental Toxicology and Chemistry. 35(5):1247-1256.

Liu, Y.W., Chan, W.K., 2002. Thyroid hormones are important for embryonic tolarval transitory phase in zebrafish. Differentiation 70, 36–45,

Maack, G., Segner, H., 2003. Morphological development of the gonads in zebrafish. Journal of Fish Biology 62, 895-906.

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.

Nagabhushana A, Mishra RK. 2016. Finding clues to the riddle of sex determination in zebrafish. Journal of Biosciences. 41(1):145-155.

Olmstead AW, Villeneuve DL, Ankley GT, Cavallin JE, Lindberg-Livingston A, Wehmas LC, Degitz SJ. 2011. A method for the determination of genetic sex in the fathead minnow, pimephales promelas, to support testing of endocrine-active chemicals. Environmental Science & Technology. 45(7):3090-3095.

Pandelides Z, Ussery EJ, Overturf MD, Guchardi J, Holdway DA. 2021. Inhibition of swim bladder inflation in japanese medaka (oryzias latipes) embryos following exposure to select pharmaceuticals alone and in combination. Aquatic Toxicology. 234.

Stinckens, E., Vergauwen, L., Ankley, G.T., Blust, R., Darras, V.M., Villeneuve, D.L., Witters, H., Volz, D.C., Knapen, D., 2018. An AOP-based alternative testing strategy to predict the impact of thyroid hormone disruption on swim bladder inflation in zebrafish. Aquatic Toxicology 200, 1-12.

van Aerle R, Runnalls TJ, Tyler CR. 2004. Ontogeny of gonadal sex development relative to growth in fathead minnow. Journal of Fish Biology. 64(2):355-369.

Wang, J.X., Shi, G.H., Yao, J.Z., Sheng, N., Cui, R.N., Su, Z.B., Guo, Y., Dai, J.Y., 2020. Perfluoropolyether carboxylic acids (novel alternatives to PFOA) impair zebrafish posterior swim bladder development via thyroid hormone disruption. Environment International 134.

Winata, C.L., Korzh, S., Kondrychyn, I., Zheng, W., Korzh, V., Gong, Z., 2009.Development of zebrafish swimbladder: the requirement of Hedgehogsignaling in specification and organization of the three tissue layers. Dev. Biol.331, 222–236,

Woolley, L.D., Qin, J.G., 2010. Swimbladder inflation and its implication to the culture of marine finfish larvae. Reviews in Aquaculture 2, 181-190.