Development of a Zebrafish Embryo-Based Test System for Thyroid Hormone System Disruption: 3Rs in Ecotoxicological Research.

Aquatic toxicology Behavioral toxicology Endocrine‐disrupting compounds Histopathology New approach methodologies

Journal

Environmental toxicology and chemistry
ISSN: 1552-8618
Titre abrégé: Environ Toxicol Chem
Pays: United States
ID NLM: 8308958

Informations de publication

Date de publication:
28 May 2024
Historique:
revised: 05 03 2024
received: 05 02 2024
accepted: 25 03 2024
medline: 28 5 2024
pubmed: 28 5 2024
entrez: 28 5 2024
Statut: aheadofprint

Résumé

There is increasing concern regarding pollutants disrupting the vertebrate thyroid hormone (TH) system, which is crucial for development. Thus, identification of TH system-disrupting chemicals (THSDCs) is an important requirement in the Organisation for Economic Co-operation and Development (OECD) testing framework. The current OECD approach uses different model organisms for different endocrine modalities, leading to a high number of animal tests. Alternative models compatible with the 3Rs (replacement, reduction, refinement) principle are required. Zebrafish embryos, not protected by current European Union animal welfare legislation, represent a promising model. Studies show that zebrafish swim bladder inflation and eye development are affected by THSDCs, and the respective adverse outcome pathways (AOPs) have been established. The present study compared effects of four THSDCs with distinct molecular modes of action: Propylthiouracil (PTU), potassium perchlorate, iopanoic acid, and the TH triiodothyronine (T3) were tested with a protocol based on the OECD fish embryo toxicity test (FET). Effects were analyzed according to the AOP concept from molecular over morphological to behavioral levels: Analysis of thyroid- and eye-related gene expression revealed significant effects after PTU and T3 exposure. All substances caused changes in thyroid follicle morphology of a transgenic zebrafish line expressing fluorescence in thyrocytes. Impaired eye development and swimming activity were observed in all treatments, supporting the hypothesis that THSDCs cause adverse population-relevant changes. Findings thus confirm that the FET can be amended by TH system-related endpoints into an integrated protocol comprising molecular, morphological, and behavioral endpoints for environmental risk assessment of potential endocrine disruptors, which is compatible with the 3Rs principle. Environ Toxicol Chem 2024;00:1-18. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Identifiants

pubmed: 38804632
doi: 10.1002/etc.5878
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : University of Heidelberg
ID : Olympia Morata Program
Organisme : European Union Horizon 2020
ID : 825753

Informations de copyright

© 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

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Auteurs

Lisa Gölz (L)

Aquatic Ecology & Toxicology, Centre for Organismal Studies, University of Heidelberg, Heidelberg, Germany.
Current affiliation: Institute of Pharmacology, University of Heidelberg, Heidelberg, Germany.

Melanie Blanc-Legendre (M)

MARBEC, Université de Montpellier, CNRS, Ifremer, IRD, INRAE, Palavas, France.

Maximilian Rinderknecht (M)

Aquatic Ecology & Toxicology, Centre for Organismal Studies, University of Heidelberg, Heidelberg, Germany.

Laura Behnstedt (L)

Aquatic Ecology & Toxicology, Centre for Organismal Studies, University of Heidelberg, Heidelberg, Germany.

Sara Coordes (S)

Aquatic Ecology & Toxicology, Centre for Organismal Studies, University of Heidelberg, Heidelberg, Germany.

Luisa Reger (L)

Aquatic Ecology & Toxicology, Centre for Organismal Studies, University of Heidelberg, Heidelberg, Germany.

Sacha Sire (S)

MARBEC, Université de Montpellier, CNRS, Ifremer, IRD, INRAE, Palavas, France.

Xavier Cousin (X)

MARBEC, Université de Montpellier, CNRS, Ifremer, IRD, INRAE, Palavas, France.

Thomas Braunbeck (T)

Aquatic Ecology & Toxicology, Centre for Organismal Studies, University of Heidelberg, Heidelberg, Germany.

Lisa Baumann (L)

Aquatic Ecology & Toxicology, Centre for Organismal Studies, University of Heidelberg, Heidelberg, Germany.
Current affiliation: Amsterdam Institute for Life and Environment, Section Environmental Health & Toxicology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Classifications MeSH