Applications of the SR4G Transgenic Zebrafish Line for Biomonitoring of Stress-Disrupting Compounds: A Proof-of-Concept Study

Transgenic zebrafish models have been successfully used in biomonitoring and risk assessment studies of environmental pollutants, including xenoestrogens, pesticides, and heavy metals. We employed zebrafish larva (transgenic SR4G line) with a cortisol-inducible green fluorescence protein reporter (e...

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Autores principales:	Amin Nozari, Selena Do, Vance L. Trudeau
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	zebrafish endocrine-disrupting compounds biomonitoring assay environmental toxicology transgenic model stress-axis Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/89abc95a8d0647b292870ddff7dfda41
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spelling	oai:doaj.org-article:89abc95a8d0647b292870ddff7dfda412021-11-17T06:13:58ZApplications of the SR4G Transgenic Zebrafish Line for Biomonitoring of Stress-Disrupting Compounds: A Proof-of-Concept Study1664-239210.3389/fendo.2021.727777https://doaj.org/article/89abc95a8d0647b292870ddff7dfda412021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fendo.2021.727777/fullhttps://doaj.org/toc/1664-2392Transgenic zebrafish models have been successfully used in biomonitoring and risk assessment studies of environmental pollutants, including xenoestrogens, pesticides, and heavy metals. We employed zebrafish larva (transgenic SR4G line) with a cortisol-inducible green fluorescence protein reporter (eGFP) as a model to detect stress responses upon exposure to compounds with environmental impact, including bisphenol A (BPA), vinclozolin (VIN), and fluoxetine (FLX). Cortisol, fluorescence signal, and mRNA levels of eGFP and 11 targeted genes were measured in a homogenized pool of zebrafish larvae, with six experimental replicates for each endpoint. Eleven targeted genes were selected according to their association with stress-axis and immediate early response class of genes. Hydrocortisone (CORT)and dexamethasone (DEX) were used as positive and negative controls, respectively. All measurements were done in two unstressed and stressed condition using standardized net handling as the stressor. A significant positive linear correlation between cortisol levels and eGFP mRNA levels was observed (r> 0.9). Based on eGFP mRNA levels in unstressed and stressed larvae two predictive models were trained (Random Forest and Logistic Regression). Both these models could correctly predict the blunted stress response upon exposure to BPA, VIN, FLX and the negative control, DEX. The negative predictive value (NPV) of these models were 100%. Similar NPV was observed when the predictive models trained based on the mRNA levels of the eleven assessed genes. Measurement of whole-body fluorescence intensity signal was not significant to detect blunted stress response. Our findings support the use of SR4G transgenic larvae as an in vivo biomonitoring model to screen chemicals for their stress-disrupting potentials. This is important because there is increasing evidence that brief exposures to environmental pollutants modify the stress response and critical coping behaviors for several generations.Amin NozariSelena DoVance L. TrudeauFrontiers Media S.A.articlezebrafishendocrine-disrupting compoundsbiomonitoring assayenvironmental toxicologytransgenic modelstress-axisDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENFrontiers in Endocrinology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	zebrafish endocrine-disrupting compounds biomonitoring assay environmental toxicology transgenic model stress-axis Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	zebrafish endocrine-disrupting compounds biomonitoring assay environmental toxicology transgenic model stress-axis Diseases of the endocrine glands. Clinical endocrinology RC648-665 Amin Nozari Selena Do Vance L. Trudeau Applications of the SR4G Transgenic Zebrafish Line for Biomonitoring of Stress-Disrupting Compounds: A Proof-of-Concept Study
description	Transgenic zebrafish models have been successfully used in biomonitoring and risk assessment studies of environmental pollutants, including xenoestrogens, pesticides, and heavy metals. We employed zebrafish larva (transgenic SR4G line) with a cortisol-inducible green fluorescence protein reporter (eGFP) as a model to detect stress responses upon exposure to compounds with environmental impact, including bisphenol A (BPA), vinclozolin (VIN), and fluoxetine (FLX). Cortisol, fluorescence signal, and mRNA levels of eGFP and 11 targeted genes were measured in a homogenized pool of zebrafish larvae, with six experimental replicates for each endpoint. Eleven targeted genes were selected according to their association with stress-axis and immediate early response class of genes. Hydrocortisone (CORT)and dexamethasone (DEX) were used as positive and negative controls, respectively. All measurements were done in two unstressed and stressed condition using standardized net handling as the stressor. A significant positive linear correlation between cortisol levels and eGFP mRNA levels was observed (r> 0.9). Based on eGFP mRNA levels in unstressed and stressed larvae two predictive models were trained (Random Forest and Logistic Regression). Both these models could correctly predict the blunted stress response upon exposure to BPA, VIN, FLX and the negative control, DEX. The negative predictive value (NPV) of these models were 100%. Similar NPV was observed when the predictive models trained based on the mRNA levels of the eleven assessed genes. Measurement of whole-body fluorescence intensity signal was not significant to detect blunted stress response. Our findings support the use of SR4G transgenic larvae as an in vivo biomonitoring model to screen chemicals for their stress-disrupting potentials. This is important because there is increasing evidence that brief exposures to environmental pollutants modify the stress response and critical coping behaviors for several generations.
format	article
author	Amin Nozari Selena Do Vance L. Trudeau
author_facet	Amin Nozari Selena Do Vance L. Trudeau
author_sort	Amin Nozari
title	Applications of the SR4G Transgenic Zebrafish Line for Biomonitoring of Stress-Disrupting Compounds: A Proof-of-Concept Study
title_short	Applications of the SR4G Transgenic Zebrafish Line for Biomonitoring of Stress-Disrupting Compounds: A Proof-of-Concept Study
title_full	Applications of the SR4G Transgenic Zebrafish Line for Biomonitoring of Stress-Disrupting Compounds: A Proof-of-Concept Study
title_fullStr	Applications of the SR4G Transgenic Zebrafish Line for Biomonitoring of Stress-Disrupting Compounds: A Proof-of-Concept Study
title_full_unstemmed	Applications of the SR4G Transgenic Zebrafish Line for Biomonitoring of Stress-Disrupting Compounds: A Proof-of-Concept Study
title_sort	applications of the sr4g transgenic zebrafish line for biomonitoring of stress-disrupting compounds: a proof-of-concept study
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/89abc95a8d0647b292870ddff7dfda41
work_keys_str_mv	AT aminnozari applicationsofthesr4gtransgeniczebrafishlineforbiomonitoringofstressdisruptingcompoundsaproofofconceptstudy AT selenado applicationsofthesr4gtransgeniczebrafishlineforbiomonitoringofstressdisruptingcompoundsaproofofconceptstudy AT vanceltrudeau applicationsofthesr4gtransgeniczebrafishlineforbiomonitoringofstressdisruptingcompoundsaproofofconceptstudy
_version_	1718425870781120512

Applications of the SR4G Transgenic Zebrafish Line for Biomonitoring of Stress-Disrupting Compounds: A Proof-of-Concept Study

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