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

PloS One
Sergio JarqueStefan Scholz

Abstract

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 a...Continue Reading

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Citations

Apr 11, 2019·International Journal of Molecular Sciences·Sergio JarqueJavier Terriente
Mar 17, 2019·International Journal of Molecular Sciences·Gunjan PandeyJochen Gehrig
Mar 10, 2020·Molecular and Cellular Endocrinology·Stephan CouderqJean-Baptiste Fini
Apr 4, 2021·Aquatic Toxicology·Keng Po LaiWilliam Ka Fai Tse
May 30, 2021·Environmental Pollution·ZhiChao DangAude Kienzler
Nov 27, 2021·Biomedical Chromatography : BMC·Burcu EserAylin Sepici Dincel

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Methods Mentioned

BETA
transgenic
fluorescence
fluorescence imaging

Software Mentioned

image J
KNIME
drc
R
R Core
VAST

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