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Impaired swim bladder inflation in early-life stage fathead minnows exposed to a deiodinase inhibitor, iopanoic acid
Cavallin, J., G. Ankley, B. Blackwell, C. Blanksma, K. Fay, K. Jensen, M. Kahl, D. Knapen, Pat Kosian, S. Poole, E. Randolph, A. Schroeder, L. Vergauwen, AND Dan Villeneuve. Impaired swim bladder inflation in early-life stage fathead minnows exposed to a deiodinase inhibitor, iopanoic acid. SETAC North America, Orlando, FL, November 06 - 10, 2016.
The thyroid axis plays a critical role in teleost fish development. The present study investigated whether inhibition of deiodinase, the enzyme which converts thyroxine (T4), to the more biologically-active form, 3,5,3'-triiodothyronine (T3), would impact inflation of the posterior and/or anterior swim bladder (SB), processes which we previously demonstrated to be thyroid-hormone regulated. Two experiments were conducted using iopanoic acid (IOP), a pharmaceutical used to treat hyperthyroidism, as a model deiodinase inhibitor. In the first study, fathead minnow (Pimephales promelas) embryos (~1 day post-fertilization [dpf]) were exposed in a flow-through system to three concentrations of IOP (0.6, 1.9, 6.0 mg/L) or control water and sampled at 4 and 6 dpf. Whole body T4 and T3 concentrations were measured using LC-MS/MS. Abundance of deiodinase 1-3 (dio1-3), thyroid-stimulating hormone (tsh), and thyroperoxidase (tpo) transcripts was examined using quantitative polymerase-chain reaction. Posterior SB inflation was assessed at 6 dpf. To examine effects on anterior SB inflation, a second study was conducted in which 6 dpf larvae, whose posterior SB had already inflated, were exposed to the same IOP concentrations. Fish were sampled at 10, 14, 18, and 21 dpf for T4/T3 measurements, gene transcription analyses, and thyroid histopathology. In the embryo study, incidence and length of inflated posterior SBs were significantly reduced in the 6.0 mg/L treatment at 6 dpf. Dose-dependent increases in T4 and T3 concentrations were measured at 4 dpf, but only T3 concentrations remained elevated until 6 dpf. Significant dose-dependent down-regulation of tpo transcript abundance was observed at 6 dpf. Incidence and length of anterior SB inflation in larval fish were significantly reduced in all IOP treatments at 14 dpf. However by 18 dpf, anterior SBs had inflated in fish from all treatments, suggesting inflation was delayed, not prevented. Significant up-regulation of dio2 mRNA was observed at 14, 18, and 21 dpf, and significant down-regulation of tpo mRNA was observed at 10, 14, and 18 dpf in all IOP treatments. Overall, exposure to IOP altered thyroid hormone concentrations, gene transcription, and swim bladder inflation in early-life stage fathead minnows.