title: Thyroid disruption in zebrafish (Danio rerio) larvae: Different molecular response patterns lead to impaired eye development and visual functions.
abstract: The vertebrate thyroid system is important for multiple developmental processes, including eye development. Thus, its environmentally induced disruption may impact important fitness-related parameters like visual capacities and behaviour. The present study investigated the relation between molecular effects of thyroid disruption and morphological and physiological changes of eye development in zebrafish (Danio rerio). Two test compounds representing different molecular modes of thyroid disruption were used: propylthiouracil (PTU), which is an enzyme-inhibitor of thyroid hormone synthesis, and tetrabromobisphenol A (TBBPA), which interacts with the thyroid hormone receptors. Both chemicals significantly altered transcript levels of thyroid system-related genes (TRα, TRβ, TPO, TSH, DIO1, DIO2 and DIO3) in a compound-specific way. Despite these different molecular response patterns, both treatments resulted in similar pathological alterations of the eyes such as reduced size, RPE cell diameter and pigmentation, which were concentration-dependent. The morphological changes translated into impaired visual performance of the larvae: the optokinetic response was significantly and concentration-dependently decreased in both treatments, together with a significant increase of light preference of PTU-treated larvae. In addition, swimming activity was impacted. This study provides first evidence that different modes of molecular action of the thyroid disruptors can be associated with uniform apical responses. Furthermore, this study is the first to show that pathological eye development, as it can be induced by exposure to thyroid disruptors, indeed translates into impaired visual capacities of zebrafish early life stages.
authors.affiliation: University of Berne, Vetsuisse Faculty, Centre for Fish and Wildlife Health, Länggassstrasse 122, CH-3012 Berne, Switzerland. Electronic address: lisa.baumann@vetsuisse.unibe.ch.
authors.forename: Lisa
authors.initials: L
authors.lastname: Baumann
authors.affiliation: University of Berne, Vetsuisse Faculty, Centre for Fish and Wildlife Health, Länggassstrasse 122, CH-3012 Berne, Switzerland. Electronic address: albert.ros@vetsuisse.unibe.ch.
authors.forename: Albert
authors.initials: A
authors.lastname: Ros
authors.affiliation: University of Berne, Vetsuisse Faculty, Centre for Fish and Wildlife Health, Länggassstrasse 122, CH-3012 Berne, Switzerland. Electronic address: kristina.rehberger@vetsuisse.unibe.ch.
authors.forename: Kristina
authors.initials: K
authors.lastname: Rehberger
authors.affiliation: University of Zurich, Institute of Molecular Life Sciences, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. Electronic address: stephan.neuhauss@imls.uzh.ch.
authors.forename: Stephan C F
authors.initials: SC
authors.lastname: Neuhauss
authors.affiliation: University of Berne, Vetsuisse Faculty, Centre for Fish and Wildlife Health, Länggassstrasse 122, CH-3012 Berne, Switzerland. Electronic address: helmut.segner@vetsuisse.unibe.ch.
authors.forename: Helmut
authors.initials: H
authors.lastname: Segner
mesh_terms: D000818:Animals; D005123:Eye / Q000187:drug effects / Q000254:growth & development; D029941:Fish Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D011441:Propylthiouracil / Q000633:toxicity*; D013961:Thyroid Gland / Q000187:drug effects*; D013963:Thyroid Hormones / Q000235:genetics; D014785:Vision, Ocular / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000633:toxicity; D015027:Zebrafish / Q000502:physiology*
chemical_list: D029941:Fish Proteins; D011075:Polybrominated Biphenyls; D013963:Thyroid Hormones; D014874:Water Pollutants, Chemical; D011441:Propylthiouracil; C020806:tetrabromobisphenol A
keywords: Behaviour; Eye development; Thyroid disruption; Zebrafish