The thyroid hormone system disrupting potential of resorcinol in fish

Environmental pollutants capable of interfering with the thyroid hormone (TH) system increasingly raise concern for both human and environmental health. Recently, resorcinol has received attention as a compound of concern due to its endocrine disrupting properties. It is a known inhibitor of thyrope...

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Main Authors: Imke Van Dingenen, Emma Andersen, Sina Volz, Monica Christiansen, Jiří Novák, Ann-Cathrin Haigis, Emma Stacy, Brett R. Blackwell, Daniel L. Villeneuve, Lucia Vergauwen, Klára Hilscherová, Henrik Holbech, Dries Knapen
Format: Article
Language:English
Published: Elsevier 2024-10-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651324010716
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author Imke Van Dingenen
Emma Andersen
Sina Volz
Monica Christiansen
Jiří Novák
Ann-Cathrin Haigis
Emma Stacy
Brett R. Blackwell
Daniel L. Villeneuve
Lucia Vergauwen
Klára Hilscherová
Henrik Holbech
Dries Knapen
author_facet Imke Van Dingenen
Emma Andersen
Sina Volz
Monica Christiansen
Jiří Novák
Ann-Cathrin Haigis
Emma Stacy
Brett R. Blackwell
Daniel L. Villeneuve
Lucia Vergauwen
Klára Hilscherová
Henrik Holbech
Dries Knapen
author_sort Imke Van Dingenen
collection DOAJ
description Environmental pollutants capable of interfering with the thyroid hormone (TH) system increasingly raise concern for both human and environmental health. Recently, resorcinol has received attention as a compound of concern due to its endocrine disrupting properties. It is a known inhibitor of thyroperoxidase (TPO), an enzyme required in TH synthesis, and therapeutic use of resorcinol exposure has led to hypothyroidism in humans. There is limited evidence concerning ecotoxicologically relevant effects of resorcinol in fish. A set of adverse outcome pathways (AOPs) has recently been developed linking thyroid hormone system disruption (THSD) to impaired swim bladder inflation and eye development in fish. In the present study, these AOPs were used to provide the background for testing potential THSD effects of resorcinol in zebrafish eleutheroembryos. We exposed zebrafish eleutheroembryos to resorcinol and assessed TH levels, swim bladder inflation and eye morphology. As a TPO inhibitor, resorcinol is expected to affect TH levels and eye morphology but not swim bladder inflation during embryonic development. Indeed, thyroxine (T4) levels were significantly decreased following resorcinol exposure. In contrast to our hypothesis, swim bladder inflation was impaired at 5 days post fertilization (dpf) and no effects on eye morphology were detected. Therefore, in vitro assays were performed to identify potential additional thyroid hormone system disruption-related mechanisms through which resorcinol may act. Two new mechanisms were identified: TH receptor (TR) antagonism and transthyretin (TTR) binding inhibition. Both of these mechanisms can plausibly be linked to impaired swim bladder inflation and could, therefore, explain the observed effect. Overall, our study contributes to the knowledge of the THSD potential of resorcinol both in vivo in the zebrafish model as well as in vitro.
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spelling doaj-art-72b38cbdd3be4fd3ab8bb5e476c8e2be2025-08-20T01:54:44ZengElsevierEcotoxicology and Environmental Safety0147-65132024-10-0128411699510.1016/j.ecoenv.2024.116995The thyroid hormone system disrupting potential of resorcinol in fishImke Van Dingenen0Emma Andersen1Sina Volz2Monica Christiansen3Jiří Novák4Ann-Cathrin Haigis5Emma Stacy6Brett R. Blackwell7Daniel L. Villeneuve8Lucia Vergauwen9Klára Hilscherová10Henrik Holbech11Dries Knapen12Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Wilrijk 2610, BelgiumDepartment of Biology, University of Southern Denmark, Odense M 5230, DenmarkDepartment of Biology, University of Southern Denmark, Odense M 5230, DenmarkDepartment of Biology, University of Southern Denmark, Odense M 5230, DenmarkRECETOX, Faculty of Science, Masaryk University, Kamenice 5, Brno 625 00, Czech RepublicZebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Wilrijk 2610, BelgiumUnited States Environmental Protection Agency, Great Lakes Toxicology and Ecology Division, Duluth, MN 55804, United StatesUnited States Environmental Protection Agency, Great Lakes Toxicology and Ecology Division, Duluth, MN 55804, United StatesUnited States Environmental Protection Agency, Great Lakes Toxicology and Ecology Division, Duluth, MN 55804, United StatesZebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Wilrijk 2610, BelgiumRECETOX, Faculty of Science, Masaryk University, Kamenice 5, Brno 625 00, Czech RepublicDepartment of Biology, University of Southern Denmark, Odense M 5230, DenmarkZebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Wilrijk 2610, Belgium; Corresponding author.Environmental pollutants capable of interfering with the thyroid hormone (TH) system increasingly raise concern for both human and environmental health. Recently, resorcinol has received attention as a compound of concern due to its endocrine disrupting properties. It is a known inhibitor of thyroperoxidase (TPO), an enzyme required in TH synthesis, and therapeutic use of resorcinol exposure has led to hypothyroidism in humans. There is limited evidence concerning ecotoxicologically relevant effects of resorcinol in fish. A set of adverse outcome pathways (AOPs) has recently been developed linking thyroid hormone system disruption (THSD) to impaired swim bladder inflation and eye development in fish. In the present study, these AOPs were used to provide the background for testing potential THSD effects of resorcinol in zebrafish eleutheroembryos. We exposed zebrafish eleutheroembryos to resorcinol and assessed TH levels, swim bladder inflation and eye morphology. As a TPO inhibitor, resorcinol is expected to affect TH levels and eye morphology but not swim bladder inflation during embryonic development. Indeed, thyroxine (T4) levels were significantly decreased following resorcinol exposure. In contrast to our hypothesis, swim bladder inflation was impaired at 5 days post fertilization (dpf) and no effects on eye morphology were detected. Therefore, in vitro assays were performed to identify potential additional thyroid hormone system disruption-related mechanisms through which resorcinol may act. Two new mechanisms were identified: TH receptor (TR) antagonism and transthyretin (TTR) binding inhibition. Both of these mechanisms can plausibly be linked to impaired swim bladder inflation and could, therefore, explain the observed effect. Overall, our study contributes to the knowledge of the THSD potential of resorcinol both in vivo in the zebrafish model as well as in vitro.http://www.sciencedirect.com/science/article/pii/S0147651324010716Thyroid hormone system disruptionswim bladder inflationeye developmentthyroid hormone levelszebrafish embryoadverse outcome pathway
spellingShingle Imke Van Dingenen
Emma Andersen
Sina Volz
Monica Christiansen
Jiří Novák
Ann-Cathrin Haigis
Emma Stacy
Brett R. Blackwell
Daniel L. Villeneuve
Lucia Vergauwen
Klára Hilscherová
Henrik Holbech
Dries Knapen
The thyroid hormone system disrupting potential of resorcinol in fish
Ecotoxicology and Environmental Safety
Thyroid hormone system disruption
swim bladder inflation
eye development
thyroid hormone levels
zebrafish embryo
adverse outcome pathway
title The thyroid hormone system disrupting potential of resorcinol in fish
title_full The thyroid hormone system disrupting potential of resorcinol in fish
title_fullStr The thyroid hormone system disrupting potential of resorcinol in fish
title_full_unstemmed The thyroid hormone system disrupting potential of resorcinol in fish
title_short The thyroid hormone system disrupting potential of resorcinol in fish
title_sort thyroid hormone system disrupting potential of resorcinol in fish
topic Thyroid hormone system disruption
swim bladder inflation
eye development
thyroid hormone levels
zebrafish embryo
adverse outcome pathway
url http://www.sciencedirect.com/science/article/pii/S0147651324010716
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