Impaired swim bladder inflation in early life stage fathead minnows exposed to a deiodinase inhibitor, iopanoic acid

Environ Toxicol Chem. 2017 Nov;36(11):2942-2952. doi: 10.1002/etc.3855. Epub 2017 Jun 28.

Abstract

Inflation of the posterior and/or anterior swim bladder is a process previously demonstrated to be regulated by thyroid hormones. We investigated whether inhibition of deiodinases, which convert thyroxine (T4) to the more biologically active form, 3,5,3'-triiodothyronine (T3), would impact swim bladder inflation. Two experiments were conducted using a model deiodinase inhibitor, iopanoic acid (IOP). First, fathead minnow embryos were exposed to 0.6, 1.9, or 6.0 mg/L or control water until 6 d postfertilization (dpf), at which time posterior swim bladder inflation was assessed. To examine anterior swim bladder inflation, a second study was conducted with 6-dpf larvae exposed to the same IOP concentrations until 21 dpf. Fish from both studies were sampled for T4/T3 measurements and gene transcription analyses. Incidence and length of inflated posterior swim bladders were significantly reduced in the 6.0 mg/L treatment at 6 dpf. Incidence of inflation and length of anterior swim bladder were significantly reduced in all IOP treatments at 14 dpf, but inflation recovered by 18 dpf. Throughout the larval study, whole-body T4 concentrations increased and T3 concentrations decreased in all IOP treatments. Consistent with hypothesized compensatory responses, deiodinase-2 messenger ribonucleic acid (mRNA) was up-regulated in the larval study, and thyroperoxidase mRNA was down-regulated in all IOP treatments in both studies. These results support the hypothesized adverse outcome pathways linking inhibition of deiodinase activity to impaired swim bladder inflation. Environ Toxicol Chem 2017;36:2942-2952. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Keywords: Adverse outcome pathway; Aquatic toxicology; Developmental toxicity; Endocrine-disrupting compounds; Thyroid disruption.

MeSH terms

  • Air Sacs / drug effects*
  • Air Sacs / physiology
  • Animals
  • Chromatography, High Pressure Liquid
  • Cyprinidae / growth & development*
  • Cyprinidae / metabolism
  • Down-Regulation / drug effects
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / physiology
  • Embryonic Development / drug effects
  • Iodide Peroxidase / antagonists & inhibitors
  • Iodide Peroxidase / genetics
  • Iodide Peroxidase / metabolism*
  • Iopanoic Acid / toxicity*
  • Larva / drug effects
  • Larva / metabolism
  • RNA, Messenger / metabolism
  • Tandem Mass Spectrometry
  • Thyroxine / analysis
  • Triiodothyronine / analysis
  • Water Pollutants, Chemical / chemistry
  • Water Pollutants, Chemical / toxicity*

Substances

  • RNA, Messenger
  • Water Pollutants, Chemical
  • Triiodothyronine
  • Iodide Peroxidase
  • Iopanoic Acid
  • Thyroxine