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Reduced, Anterior swim bladder inflation leads to Reduced, Swimming performance
Key Event Relationship Overview
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 anterior swim bladder inflation||adjacent||Moderate||Low||Arthur Author (send email)||Under Development: Contributions and Comments Welcome||WPHA/WNT Endorsed|
|Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation||adjacent||Moderate||Low||Allie Always (send email)||Under Development: Contributions and Comments Welcome||WPHA/WNT Endorsed|
|Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation||adjacent||Moderate||Low||Evgeniia Kazymova (send email)||Under Development: Contributions and Comments Welcome||WPHA/WNT Endorsed|
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 increased mortality.
Evidence Collection Strategy
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.
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., 2020) 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.
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. This is in part due to the complexity of the swim bladder system and the difficulty of distinguishing effects resulting from altered anterior chamber inflation from those resulting from altered posterior chamber inflation. Additionally, swimming capacity can be affected via other processes which may or may not depend on the HPT axis, such as general malformations, 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 increased mortality 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).
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Taxonomic: Importance of proper functioning of the swim bladder for supporting natural swimming behaviour can be plausibly assumed to be generally applicable to fish possessing an anterior chamber. Evidence exists for the role of the posterior chamber in swimming performance comes from a wide variety of freshwater and marine fish species. Evidence for the specific role of the anterior chamber is however less abundant.
Life stage: In zebrafish, the anterior chamber inflates around 21 days post fertilization (dpf) which is during the larval stage. In the fathead minnow, the anterior chamber inflates around 14 dpf, also during the larval stage. Therefore this KER is only applicable to the larval life stage. To what extent fish can survive and swim with partly inflated swim bladders during later life stages is unknown.
Sex: This KER plausibly applicable to both sexes. Sex differences are not often investigated in tests using early life stages of fish. For zebrafish and fathead minnow, it is currently unclear whether sex-related differences are important in determining the magnitude of the changes in this KER. Different fish species have different sex determination and differentiation strategies. Zebrafish do not have identifiable heteromorphic sex chromosomes and sex is determined by multiple genes and influenced by the environment (Nagabhushana and Mishra, 2016). 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 21 days post fertilization in zebrafish, 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 anterior chamber inflates around 14 days post fertilization (9 dph) in fathead minnows, sex differences are expected to play a minor role in the current KER.
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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.
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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.
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