Impaired anterior swim bladder inflation following exposure to the thyroid peroxidase inhibitor 2-mercaptobenzothiazole part II: Zebrafish

Evelyn Stinckens, Lucia Vergauwen, Anthony L. Schroeder, Walid Maho, Brett R. Blackwell, Hilda Witters, Ronny Blust, Gerald T. Ankley, Adrian Covaci, Daniel L. Villeneuve, Dries Knapen

    Research output: Contribution to journalArticlepeer-review

    33 Scopus citations

    Abstract

    Disruption of the thyroid hormone (TH) system, an important mode of action, can lead to ecologically relevant adverse outcomes, especially during embryonic development. The present study characterizes the effects of disruption of TH synthesis on swim bladder inflation during zebrafish early-life stages using 2-mercaptobenzothiazole (MBT), a thyroid peroxidase (TPO) inhibitor. Zebrafish were exposed to different MBT concentrations until 120/168 h post fertilization (hpf) and 32 days post fertilization (dpf), in two sets of experiments, to investigate the effects of TPO inhibition on posterior and anterior swim bladder inflation respectively, as well as whole body thyroid hormone concentrations (triiodothyronine (T3) and its prohormone, thyroxine (T4)). At 120 hpf, MBT did not directly impair posterior chamber inflation or size, while anterior chamber inflation and size was impaired at 32 dpf. As previously shown in amphibians and mammals, we confirmed that MBT inhibits TPO in fish. Whole-body T4 decreased after MBT exposure at both time points, while T3 levels were unaltered. There was a significant relationship between T4 levels and the anterior chamber surface at 32 dpf. The absence of effects on posterior chamber inflation can possibly be explained by maternal transfer of T4 into the eggs. These maternally derived THs are depleted at 32 dpf and cannot offset TPO inhibition, resulting in impaired anterior chamber inflation. Therefore, we hypothesize that TPO inhibition only inhibits swim bladder inflation during late development, after depletion of maternally derived T4. In a previous study, we showed that iodothyronine deiodinase (ID) knockdown impaired posterior chamber inflation during early development. Our findings, in parallel with similar effects observed in fathead minnow (see part I, this issue) suggest that thyroid disruption impacts swim bladder inflation, and imply an important distinction among specific subtypes of TH disrupting chemicals. However, the existence of another - yet unknown - mode of action of MBT impacting swim bladder inflation cannot be excluded. These results can be helpful for delineating adverse outcome pathways (AOPs) linking TPO inhibition, ID inhibition and other TH related molecular initiating events, to impaired swim bladder inflation in fish during early life stages. Such AOPs can support the use of in vitro enzyme inhibition assays for predicting reduced survival due to impaired posterior and anterior chamber inflation.

    Original languageEnglish (US)
    Pages (from-to)204-217
    Number of pages14
    JournalAquatic Toxicology
    Volume173
    DOIs
    StatePublished - Apr 1 2016

    Bibliographical note

    Funding Information:
    This work was funded by the Cefic Long-range Research Initiative ( http://www.cefic-lri.org/ ) project LRI-ECO20-UA (Development of an alternative testing strategy for the fish early life-stage test for predicting chronic toxicity) with support of ECETOC. The views expressed in this paper are those of the authors and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.

    Publisher Copyright:
    © 2016 Elsevier B.V.

    Copyright:
    Copyright 2017 Elsevier B.V., All rights reserved.

    Keywords

    • 2-Mercaptobenzothiazole
    • Adverse outcome pathway
    • Fish early-life stage
    • Swim bladder inflation
    • Thyroid disruption
    • Zebrafish embryo

    Fingerprint Dive into the research topics of 'Impaired anterior swim bladder inflation following exposure to the thyroid peroxidase inhibitor 2-mercaptobenzothiazole part II: Zebrafish'. Together they form a unique fingerprint.

    Cite this