Relationship: 1034



Reduced, Anterior swim bladder inflation leads to Reduced, Swimming performance

Upstream event


Reduced, Anterior swim bladder inflation

Downstream event


Reduced, Swimming performance

Key Event Relationship Overview


AOPs Referencing Relationship


Taxonomic Applicability


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

Sex Applicability


Life Stage Applicability


Key Event Relationship Description


Effects on swim bladder inflation can alter swimming performance and buoyancy of fish, which is essential for predator avoidance, energy sparing, migration, reproduction and feeding behaviour, resulting in lower young-of-year survival.

Evidence Supporting this KER


The weight of evidence supporting a direct linkage between these two KEs, i.e. reduced anterior swim bladder inflation and reduced swimming performance, is weak.

Biological Plausibility


The anterior chamber of the swim bladder has a function in regulating the buoyancy of fish, by altering the volume of the swim bladder (Roberston et al., 2007). Fish rely on the lipid and gas content in their body to regulate their position within the water column, with the latter being more efficient at increasing body buoyancy. Therefore, fish with functional swim bladders have no problem supporting their body (Brix 2002), while it is highly likely that impaired inflation severely impacts swimming performance. Fish with no functional swim bladder can survive, but are severely disadvantaged., making the likelihood of surviving smaller.

Several studies in zebrafish and fathead minnow showed that a smaller AC was associated with a larger posterior chamber (Nelson et al., 2016; Stinckens et al., 2016; Cavallin et al., 2017, Stinckens et al., submitted) suggesting a possible compensatory mechanism. As shown by Stoyek et al. (2011) however, the AC volume is highly dynamic under normal conditions due to a series of regular corrugations running along the chamber wall, and is in fact the main driver for adjusting buoyancy while the basic PC volume remains largely invariable. Therefore, it is plausible to assume that functionality of the swim bladder is affected when AC inflation is incomplete, even when the PC appears to fully compensate the gas volume of the swim bladder.

Empirical Evidence


  • Lindsey et al. (2010) showed that zebrafish started swimming deeper down in the water column upon inflation of the anterior chamber, confirming a role of the anterior chamber in supporting swimming performance.
  • After exposure to 2-mercaptobenzothiazole, a TPO inhibitor, from 0 to 32 days post fertilization (dpf) in zebrafish, the swimming activity of fish was impacted starting at 26 dpf if the inflation of the anterior chamber of the swim bladder was impaired or had no normal structure/size (Stinckens et al., 2016).
  • Methimazole (MMI) and propylthiouracil (PTU), two thyroperoxidase inhibitors, and  iopanoic acid (IOP), a deiodinase inhibitor, each reduced both anterior chamber inflation and swimming distance in zebrafish exposed from fertlization until the age of 32 days (Stinckens et al., 2020). Stinckens et al. (2020) showed a specific, direct link between reduced anterior chamber inflation and reduced swimming performance. First, after 21 d of exposure to 111 mg/L propylthiouracil around 30% of anterior chambers were not inflated and swimming distance was reduced, while by 32 days post fertilization all larvae had successfully inflated their anterior chamber and the effect on swimming distance had disappeared. The most direct way to assess the role of anterior chamber inflation in swimming performance, however, is to compare larvae with and without inflated anterior chamber at the same time point and within the same experimental treatment. Both in the propylthiouracil exposure at 21 days post fertilization and in the iopanoic acid exposure at 21 and 32 days post fertilization, swimming distance was clearly reduced in larvae lacking an inflated anterior chamber, while the swimming distance of larvae with inflated anterior chamber was equal to that of controls.
  • It has also been reported that larvae that fail to inflate their swim bladder use additional energy to maintain buoyancy (Lindsey et al., 2010, Goodsell et al. 1996), possibly contributing to reduced swimming activity. Furthermore, Chatain (1994) associated larvae with non-inflated swim bladders with numerous complications, such as spinal deformities and lordosis and reduced growth rates, adding to the impact on swimming behaviour.
  • An increasing incidence of swim bladder non-inflation has also been reported in Atlantic salmon (Poppe et al. 1997). Affected fish had severely altered balance and buoyancy, observed through a specific swimming behaviour, as the affected fish were swimming upside down in an almost vertical position (Poppe et al. 1997).

Uncertainties and Inconsistencies


After exposure to 100 mg/L methimazole, 95% of the zebrafish larvae failed to inflate their anterior chamber at 32 dpf and swimming distance was reduced (Stinckens et al., 2020). On the other hand, there was no effect of impaired anterior chamber inflation on swimming distance in the methimazole exposure of 50 mg/L. Also, inflated but smaller anterior chambers did not result in a decreased swimming performance in this study. A similar result, where non-inflated anterior chambers did not consistently lead to reduced swimming performance, was previously found after exposure to 2-mercaptobenzothiazole (Stinckens et al., 2016). In summary, the precise relationship between these two KEs is not easy to determine and may be different for different chemicals. Swimming capacity can be affected via other processes which may or may not depend on the HPT axis, such as decreased cardiorespiratory function, energy metabolism and growth.

As Robertson et al., (2007) reported, the swim bladder only starts regulating buoyancy actively from 32 dpf onward in zebrafish, possibly explaining the lack of effect on swimming capacity in some cases.

The anterior chamber is also important for producing and transducing sound through the Weberian Apparatus (Popper, 1974; Lechner and Ladich, 2008). It is highly plausible that impaired inflation or size of the anterior swim bladder could lead to a reduction in young-of-year survival as hearing loss would affect their ability to respond to their surrounding environment, thus impacting ecological relevant endpoints such as predator avoidance or prey seeking (Wisenden et al., 2008; Fay, 2009).



Quantitative Understanding of the Linkage


The direct quantitative evidence supporting the connection between anterior chamber impairment and swimming capacity is lacking.

Response-response Relationship




Known modulating factors


Known Feedforward/Feedback loops influencing this KER


Domain of Applicability


Importance of swimming performance for natural behaviour is generally applicable to fish.



Brix O (2002) The physiology of living in water. In: Hart PJ, Reynolds J (eds) Handbook of Fish Biology and Fisheries, Vol. 1, pp. 70–96. Blackwell Publishing, Malden, USA.

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.

Chatain, B., 1994. Abnormal swimbladder development and lordosis in sea bass (Dicentrarchus labrax) and sea bream (Sparus auratus). Aquaculture 119:371–379.

Czesny, S.J., Graeb, B.D.S., Dettmersn, J.M., 2005. Ecological consequences of swimbladder noninflation for larval yellow perch. Trans. Am. Fish. Soc. 134,1011–1020, http://dx.doi.org/10.1577/T04-016.1.

Fay, R., 2009. Soundscapes and the sense of hearing of fishes. Integrative Zool. 4,26–32.

Goodsell, D.S., Morris, G.M., Olsen, A.J. 1996. Automated docking of fleixble ligands. Applications of Autodock. J. Mol. Recogonition, 9:1-5.

Kurata, M., Ishibashi, Y., Takii, K., Kumai, H., Miyashita, S., Sawada, Y., 2014.Influence of initial swimbladder inflation failure on survival of Pacific bluefintuna, Thuunus orientalis (Temminck and Schlegl) larvae. Aquacult. Res. 45,882–892.

Lechner, W., Ladich, F., 2008. Size matters: diversity in swimbladders andWeberian ossicles affects hearing in catfishes. J. Exp. Biol. 211, 1681–1689.

Lindsey, B.W., Smith, F.M., Croll, R.P., 2010. From inflation to flotation: contribution of the swimbladder to whole-body density and swimming depth during development of the zebrafish (Danio rerio). Zebrafish 7, 85–96, http://dx.doi.org/10.1089/zeb.2009.0616.

Nelson, K., Schroeder, A., Ankley, G., Blackwell, B., Blanksma, C., Degitz, S., Flynn, K., Jensen, K., Johnson, R., Kahl, M., Knapen, D., Kosian, P., Milsk, R., Randolph, E., Saari, T., Stinckens, E., Vergauwen, L., Villeneuve, D., 2016. Impaired anterior swim bladder inflation following exposure to the thyroid peroxidase inhibitor 2-mercaptobenzothiazole part I: Fathead minnow. Aquatic Toxicology 173, 192-203.

Poppe, T.T., Hellberg, H., Griffiths, D., Mendal, H. 1977. Swim bladder abnormality in farmed Atlantic salmon, Salmo salar. Diseases of aquatic organisms 30:73-76.

Roberston, G.N., McGee, C.A.S., Dumbarton, T.C., Croll, R.P., Smith, F.M., 2007.Development of the swim bladder and its innervation in the zebrafish, Danio rerio. J. Morphol. 268, 967–985, http://dx.doi.org/10.1002/jmor.

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.

Stinckens, E., Vergauwen, L., Schroeder, A.L., Maho, W., Blackwell, B., Witter, H.,Blust, R., Ankley, G.T., Covaci, A., Villenueve, D.L., Knapen, D., 2016. Disruption of thyroid hormone balance after 2-mercaptobenzothiazole exposure causes swim bladder inflation impairment—part II: zebrafish. Aquat. Toxicol. 173:204-17.

Stoyek, M.R., Smith, F.M., Croll, R.P., 2011. Effects of altered ambient pressure on the volume and distribution of gas within the swimbladder of the adult zebrafish, Danio rerio. Journal of Experimental Biology 214, 2962-2972.

Wisenden, B.D., Pogatschnik, J., Gibson, D., Bonacci, L., Schumacher, A., Willet, A.,2008. Sound the alarm: learned association of predation risk with novelauditory stimuli by fathead minnows (Pimephales promelas) and glowlighttetras (Hemigrammus erythrozonus) after single simultaneous pairings withconspecific chemical alarm cues. Environ. Biol. Fish 81, 141–147.

Woolley, L.D., Qin, J.G., 2010. Swimbladder inflation and its implication to theculture of marine finfish larvae. Rev. Aquac. 2, 181–190, http://dx.doi.org/10.1111/j.1753-5131.2010.01035.x.