Publication details

An automated screening method for detecting compounds with goitrogenic activity using transgenic zebrafish embryos

Authors

JARQUE ORTIZ Sergio FETTER Eva VENEMAN Wouter J. SPAINK Herman P. PERAVALI Ravindra STRAEHLE Uwe SCHOLZ Stefan

Year of publication 2018
Type Article in Periodical
Magazine / Source Plos one
MU Faculty or unit

Faculty of Science

Citation
Web Full Text
Doi http://dx.doi.org/10.1371/journal.pone.0203087
Keywords THYROID-GLAND; TOXICITY TEST; FISH; EXPRESSION; DISRUPTION; POLLUTANTS; CHEMICALS; EXPOSURE; MODEL; ASSAY
Description The knowledge on environmentally relevant chemicals that may interfere with thyroid signaling is scarce. Here, we present a method for the screening of goitrogens, compounds that disrupt the thyroid gland function, based on the automatic orientation of zebrafish in a glass capillary and a subsequent imaging of reporter gene fluorescence in the thyroid gland of embryos of the transgenic zebrafish line tg(tg:mCherry). The tg(tg:mCherry) reporter gene indicates a compensatory upregulation of thyroglobulin, the thyroid hormone precursor, in response to inhibition of thyroid hormone synthesis. Fish embryos were exposed to a negative control compound (3,4-dichloroaniline), or a concentration series of known goitrogenic compounds (resorcinol, methimazole, potassium perchlorate, 6-propyl-2-thiouracil, ethylenethiourea, phloroglucinol, pyrazole) with maximum exposure concentration selected based on mortality and/or solubility. Exposure to 3,4-dichloroaniline decreased the fluorescence signal. All goitrogenic compounds exhibited clear concentration-dependent inductions of reporter fluorescence 1.4 to 2.6 fold above control levels. Concentration-response modelling was used to calculate goitrogenic potencies based on EC50 values. The new automated method offers an efficient screening approach for goitrogenic activity.
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