Upstream eventDecreased, Triiodothyronine (T3) in serum
Reduced, Anterior swim bladder inflation
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding|
|Deiodinase 2 inhibition leading to reduced young of year survival via anterior swim bladder inflation||adjacent|
|Deiodinase 1 inhibition leading to reduced young of year survival via anterior swim bladder inflation||adjacent|
|fathead minnow||Pimephales promelas||NCBI|
Life Stage Applicability
Key Event Relationship Description
Thyroid hormones are known to be involved in development, especially in metamorphosis in amphibians and in embryonic-to-larval transition and larval-to-juvenile transition in fish. Inflation of the anterior swim bladder chamber is part of the larval-to-juvenile transition in fish, together with the development of adult fins and fin rays, ossification of the axial skeleton, formation of an adult pigmentation pattern, scale formation, maturation and remodeling of organs including the lateral line, nervous system, gut and kidneys.
Evidence Supporting this KER
Thyroid hormones are known to be involved in development, especially in metamorphosis in amphibians and in embryonic-to-larval transition (Liu and Chan, 2002) and larval-to-juvenile transition (Brown et al., 1997) in fish. Inflation of the anterior swim bladder chamber is part of the larval-to-juvenile transition in fish, together with the development of adult fins and fin rays, ossification of the axial skeleton, formation of an adult pigmentation pattern, scale formation, maturation and remodeling of organs including the lateral line, nervous system, gut and kidneys (Brown, 1997; Liu and Chan, 2002; McMenamin and Parichy, 2013).
- In a study in which embryo-larval fathead minnows (Pimephales promelas) were exposed to the thyroid peroxidase inhibitor 2-mercaptobenzothiazole (MBT), T3 concentrations measured at 14dpf were reduced at the same concentration (1 mg/L) that significantly reduced anterior swim bladder inflation at the same time-point (Nelson et al. 2016).
- Maternal injection of T3, resulting in increased T3 concentrations in the eggs of striped bass (Morone saxatilis) lead to significant increases in both swim bladder inflation and survival (Brown et al., 1988).
- In the study of Cavallin et al. (2017) fathead minnow larvae were exposed to IOP, a model iodothyronine deiodinase inhibitor that is assumed to inhibit all three deiodinase enzymes (DIO1,2,3). The authors observed pronounced decreases of whole body T3 concentrations and increases of whole body T4 concentrations, together with impaired inflation of the anterior swim bladder chamber. More specifically, inflation was delayed and the size of the swim bladder chamber was reduced until the end of the exposure experiment. Since exposure was started after inflation of the posterior chamber, this study shows that DIO inhibition can directly affect anterior chamber inflation.
Uncertainties and Inconsistencies
- Li et al. (2011) reported impairment of swim bladder inflation in Chinese rare minnows (Gobiocypris rarus) exposed to exogenous T3.
Quantitative Understanding of the Linkage
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
This KER is probably not sex-dependent since both females and males rely on THs for regulation of vital processes. Additionally, zebrafish are undifferentiated gonochorists, and gonad differentiation starts only around 23-25 dpf (Uchida et al., 2002), after the time point of anterior chamber inflation (around 21 dpf).
- 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
- Brown, D.D., 1997. The role of thyroid hormone in zebrafish and axolotl development. Proceedings of the National Academy of Sciences of the United States of America 94, 13011-13016.
- 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.
- Li W, Zha J, Yang L, Li Z, Wang Z. Regulation of thyroid hormone related genes mRNA expression by exogenous T₃ in larvae and adult Chinese rare minnow (Gobiocypris rarus). Environ Toxicol Pharmacol. 2011 Jan;31(1):189-97. doi: 10.1016/j.etap.2010.10.007.
- Liu, Y.W., Chan, W.K., 2002. Thyroid hormones are important for embryonic to larval transitory phase in zebrafish. Differentiation 70, 36-45.
- McMenamin, S.K., Parichy, D.M., 2013. Metamorphosis in Teleosts. Animal Metamorphosis 103, 127-165.
- Nelson KR, Schroeder AL, Ankley GT, Blackwell BR, Blanksma C, Degitz SJ, Flynn KM, Jensen KM, Johnson RD, Kahl MD, Knapen D, Kosian PA, Milsk RY, Randolph EC,Saari T, Stinckens E, Vergauwen L, Villeneuve DL. Impaired anterior swim bladder inflation following exposure to the thyroid peroxidase inhibitor 2-mercaptobenzothiazole part I: Fathead minnow. Aquat Toxicol. 2016 Apr;173:192-203. doi: 10.1016/j.aquatox.2015.12.024.
- Uchida, D., Yamashita, M., Kitano, T., Iguchi, T., 2002. Oocyte apoptosis during the transition from ovary-like tissue to testes during sex differentiation of juvenile zebrafish. Journal of Experimental Biology 205, 711-718.