PUBLICATION

AOP Report: Thyroperoxidase Inhibition Leading to Altered Visual Function in Fish via Altered Retinal Layer Structure

Authors
Gölz, L., Baumann, L., Pannetier, P., Braunbeck, T., Knapen, D., Vergauwen, L.
ID
ZDB-PUB-220810-3
Date
2022
Source
Environmental toxicology and chemistry   41(11): 2632-2648 (Review)
Registered Authors
Braunbeck, Thomas, Knapen, Dries, Vergauwen, Lucia
Keywords
adverse outcome pathway, ecotoxicology, endocrine disrupting compounds, eye development, thyroid hormones, zebrafish
MeSH Terms
  • Adverse Outcome Pathways*
  • Animals
  • Iodide Peroxidase*/metabolism
  • Thyroid Gland
  • Thyroid Hormones/metabolism
  • Zebrafish/metabolism
PubMed
35942927 Full text @ Environ. Toxicol. Chem.
Abstract
Thyroid hormones (THs) are involved in the regulation of many important physiological and developmental processes, including vertebrate eye development. TH system disrupting chemicals (THSDCs) may have severe consequences, as proper functioning of the visual system is a key factor for survival in wildlife. However, the sequence of events leading from TH system disruption (THSD) to altered eye development in fish has not been fully described yet. The development of this adverse outcome pathway (AOP) was based on an intensive literature review of studies that focused on THSD and impacts on eye development, mainly in fish. In total, about 120 studies (until end of 2021) were used in the development of this AOP linking inhibition of the key enzyme for TH synthesis, thyroperoxidase (TPO), to effects on retinal layer structure and visual function in fish (AOP-Wiki, AOP #363). In a weight-of-evidence (WoE) evaluation, the confidence levels were overall moderate with ample studies showing the link between reduced TH levels and altered retinal layer structure. However, some uncertainties about underlying mechanism(s) remain. While the current WoE evaluation is based on fish, the AOP is plausibly applicable to other vertebrate classes. Through the re-use of several building blocks, this AOP is connected to the AOPs leading from TPO and deiodinase inhibition to impaired swim bladder inflation in fish (AOPs #155-159), together forming an AOP network describing THSD in fish. This AOP network addresses the lack of thyroid-related endpoints in existing fish test guidelines for the evaluation of THSDCs. This article is protected by copyright. All rights reserved. © 2022 SETAC.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping