Disruption of thyroid hormone signaling is a form of endocrine disruption that is of concern to both human health and ecosystems. Research is being conducted to define the biological targets chemicals may interact with to disrupt thyroid hormone signaling and the stages in development where that disruption can most readily lead to adverse effects. The present data characterize the expression of key genes associated with thyroid hormone signaling and regulation over the course of development for two small fish widely used in aquatic ecotoxicology research. These data provide baseline information that can lead to a more complete understanding of which thyroid disrupting chemicals fish may be susceptible to and at which stages in development. This dataset is associated with the following publication: Vergauwen, L., J. Cavallin, G. Ankley, C. Bars, I. Gabriels, E. Michiels, K. Nelson, J. Periz-Stanacev, E. Randolph, S. Robinson, T. Saari, A. Schroeder, E. Stinckens, J. Swintek, S. Van Cruchten, E. Verbueken, D. Villeneuve, and D. Knapen. Gene transcription ontogeny of thyroid-axis development in early-life stage fathead minnow and zebrafish. Journal of Experimental Biology. The Company of Biologists LIMITED, Cambridge, UK, 266: 878-1002, (2018).

Supplemental materials for "The thyroid hormone system disrupting potential of resorcinol in fish". This dataset is associated with the following publication: Van Dingenen, I., E. Andersen, S. Volz, M. Christiansen, J. Novak, A. Haigis, E. Stacy, B. Blackwell, D. Villeneuve, L. Vergauwen, H. Klara, H. Holbech, and D. Knapen. The thyroid hormone system disrupting potential of resorcinol in fish. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY. Elsevier Science Ltd, New York, NY, USA, 284: 116995, (2024).

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 chamber of the swim bladder, processes previously demonstrated to be thyroid-hormone regulated. Two experiments were conducted using a model deiodinase inhibitor, iopanoic acid (IOP). In the first study, fathead minnow (Pimephales promelas) embryos were exposed to 0.6, 1.9, or 6.0 mg IOP/L or control water in a flow-through system until reaching 6 days post-fertilization (dpf) at which time posterior swim bladder inflation was assessed. To examine effects on anterior swim bladder inflation, a second study was conducted with 6 dpf larvae exposed to the same IOP concentrations until reaching 21 dpf. Fish from both studies were sampled for T4/T3 measurements, gene transcription analyses, and thyroid histopathology. In the embryo study, 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 in larval fish were significantly reduced in all IOP treatments at 14 dpf, but inflation recovered by 18 dpf. Throughout the larval study, whole body T4 concentrations were significantly increased and T3 concentrations were significantly decreased in all IOP treatments. Consistent with hypothesized compensatory responses, significant up-regulation of deiodinase-2 mRNA was observed in the larval study, and down-regulation of thyroperoxidase mRNA was observed in all IOP treatments in both studies. Taken together, these results support the hypothesized adverse outcome pathways linking inhibition of deiodinase activity to impaired swim bladder inflation. This dataset is associated with the following publication: Cavallin, J., G. Ankley, B. Blackwell, C. Blanksma, K. Fay, K. Jensen, M. Kahl, D. Knapen, P. Kosian, S. Poole, E. Randolph, A. Schroeder, L. Vergauwen, and D. Villeneuve. Impaired swim bladder inflation in early-life stage fathead minnows exposed to a deiodinase inhibitor, iopanoic acid (article). ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 36(11): 2942-2952, (2017).

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 chamber of the swim bladder, processes previously demonstrated to be thyroid-hormone regulated. Two experiments were conducted using a model deiodinase inhibitor, iopanoic acid (IOP). In the first study, fathead minnow (Pimephales promelas) embryos were exposed to 0.6, 1.9, or 6.0 mg IOP/L or control water in a flow-through system until reaching 6 days post-fertilization (dpf) at which time posterior swim bladder inflation was assessed. To examine effects on anterior swim bladder inflation, a second study was conducted with 6 dpf larvae exposed to the same IOP concentrations until reaching 21 dpf. Fish from both studies were sampled for T4/T3 measurements, gene transcription analyses, and thyroid histopathology. In the embryo study, 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 in larval fish were significantly reduced in all IOP treatments at 14 dpf, but inflation recovered by 18 dpf. Throughout the larval study, whole body T4 concentrations were significantly increased and T3 concentrations were significantly decreased in all IOP treatments. Consistent with hypothesized compensatory responses, significant up-regulation of deiodinase-2 mRNA was observed in the larval study, and down-regulation of thyroperoxidase mRNA was observed in all IOP treatments in both studies. Taken together, these results support the hypothesized adverse outcome pathways linking inhibition of deiodinase activity to impaired swim bladder inflation. This dataset is associated with the following publication: Cavallin, J., G. Ankley, B. Blackwell, C. Blanksma, K. Fay, K. Jensen, M. Kahl, D. Knapen, P. Kosian, S. Poole, E. Randolph, A. Schroeder, L. Vergauwen, and D. Villeneuve. Impaired swim bladder inflation in early-life stage fathead minnows exposed to a deiodinase inhibitor, iopanoic acid (article). ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 36(11): 2942-2952, (2017).

This file contains summary data of thyroid hormones in serum and brain in rat dams and their pups following maternal exposure to a perflorinated substance, PFHxS and an antimicrobial, Triclosan. Gene expression in thyroid glands and liver and brain were investigated. Anatomical and bahavioral indices of developmental neurotoxicity were assessed. Result so fall of these inquiries are summarized in these datasets. This dataset is associated with the following publication: Gilbert, M.E., K. OShaughnessy, S. Thomas, C. Riutta, C. Wood, A. Smith, W. Oshiro, J. Ford, A. Hotchkiss, I. Hassan, and R.L. Ford. Thyroid Disruptors: Extrathyroidal Sites of Chemical Action and Neurodevelopmental Outcome-An Examination Using Triclosan and Perfluorohexane Sulfonate. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 183(6): 195-213, (2021).

This file contains summary data of thyroid hormones in serum and brain in rat dams and their pups following maternal exposure to a perflorinated substance, PFHxS and an antimicrobial, Triclosan. Gene expression in thyroid glands and liver and brain were investigated. Anatomical and bahavioral indices of developmental neurotoxicity were assessed. Result so fall of these inquiries are summarized in these datasets. This dataset is associated with the following publication: Gilbert, M.E., K. OShaughnessy, S. Thomas, C. Riutta, C. Wood, A. Smith, W. Oshiro, J. Ford, A. Hotchkiss, I. Hassan, and R.L. Ford. Thyroid Disruptors: Extrathyroidal Sites of Chemical Action and Neurodevelopmental Outcome-An Examination Using Triclosan and Perfluorohexane Sulfonate. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 183(6): 195-213, (2021).

This dataset contains in vitro and in vivo biochemical and apical (i.e., growth/development) data pertaining to iodotyrosine deiodinase inhibition in the African clawed frog (Xenopus laevis). This dataset is associated with the following publication: Haselman, J., J. Olker, P. Kosian, J. Korte, J. Denny, J. Tietge, M. Hornung, and S. Degitz. Characterization of the Mechanistic Linkages Between Iodothyronine Deiodinase Inhibition and Impaired Thyroid-Mediated Growth and Development in Xenopus Laevis Using Iopanoic Acid. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 187(1): 139-149, (2022).

This dataset contains in vitro and in vivo biochemical and apical (i.e., growth/development) data pertaining to iodotyrosine deiodinase inhibition in the African clawed frog (Xenopus laevis). This dataset is associated with the following publication: Haselman, J., J. Olker, P. Kosian, J. Korte, J. Denny, J. Tietge, M. Hornung, and S. Degitz. Characterization of the Mechanistic Linkages Between Iodothyronine Deiodinase Inhibition and Impaired Thyroid-Mediated Growth and Development in Xenopus Laevis Using Iopanoic Acid. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 187(1): 139-149, (2022).

Adequate levels of thyroid hormones (TH) are needed for proper brain development, deficiencies may lead to adverse neurological outcomes in humans and animal models. Environmental chemicals have been linked to TH disruption, yet the relationship between developmental exposures and decline in serum TH resulting in neurodevelopmental impairment is poorly understood. The present study developed a quantitative adverse outcome pathway (qAOP) where serum thyroxin (T4) reduction following inhibition of thyroperoxidase in the thyroid gland are described and related to deficits in fetal brain TH and the development of a brain malformation, subcortical band heterotopia. Pregnant dams were exposed to 6-propylthiouracil (PTU 0, 0.1, 0.5, 1, 2, or 3 ppm) from gestational day 6-20, increasing PTU concentrations in maternal thyroid gland and serum as well as in fetal serum. Dams exposed to 0.5 ppm PTU and higher exhibited dose-dependent decreases in thyroidal T4. Serum T4 levels in the dam were significantly decreased with exposure to 2 and 3 ppm PTU. In the fetus, T4 decrements were first observed at a lower dose of 0.5 ppm PTU. Based on these data, fetal brain T4 levels were estimated from published literature sources, and quantitatively linked to increases in the size of the heterotopia present in the brains of offspring. These data show the potential of in vivo assessments and computational descriptions of biological responses to predict the development of this structural brain malformation and use of qAOP approach to evaluate brain deficits that may result from exposure to other TH disruptors. This dataset is associated with the following publication: Hassan, I., H. El-Masri, P. Kosian, J. Ford, S. Degitz, and M. Gilbert. Neurodevelopment and Thyroid Hormone Synthesis Inhibition in the Rat: Quantitative Understanding Within the Adverse Outcome Pathway Framework. TOXICOLOGICAL SCIENCES. Society of Toxicology, 57-73, (2017).

Adequate levels of thyroid hormones (TH) are needed for proper brain development, deficiencies may lead to adverse neurological outcomes in humans and animal models. Environmental chemicals have been linked to TH disruption, yet the relationship between developmental exposures and decline in serum TH resulting in neurodevelopmental impairment is poorly understood. The present study developed a quantitative adverse outcome pathway (qAOP) where serum thyroxin (T4) reduction following inhibition of thyroperoxidase in the thyroid gland are described and related to deficits in fetal brain TH and the development of a brain malformation, subcortical band heterotopia. Pregnant dams were exposed to 6-propylthiouracil (PTU 0, 0.1, 0.5, 1, 2, or 3 ppm) from gestational day 6-20, increasing PTU concentrations in maternal thyroid gland and serum as well as in fetal serum. Dams exposed to 0.5 ppm PTU and higher exhibited dose-dependent decreases in thyroidal T4. Serum T4 levels in the dam were significantly decreased with exposure to 2 and 3 ppm PTU. In the fetus, T4 decrements were first observed at a lower dose of 0.5 ppm PTU. Based on these data, fetal brain T4 levels were estimated from published literature sources, and quantitatively linked to increases in the size of the heterotopia present in the brains of offspring. These data show the potential of in vivo assessments and computational descriptions of biological responses to predict the development of this structural brain malformation and use of qAOP approach to evaluate brain deficits that may result from exposure to other TH disruptors. This dataset is associated with the following publication: Hassan, I., H. El-Masri, P. Kosian, J. Ford, S. Degitz, and M. Gilbert. Neurodevelopment and Thyroid Hormone Synthesis Inhibition in the Rat: Quantitative Understanding Within the Adverse Outcome Pathway Framework. TOXICOLOGICAL SCIENCES. Society of Toxicology, 57-73, (2017).