Comprehensive identification of gene expression fingerprints and biomarkers of sexual endocrine disruption in zebrafish embryo

Endocrine disruptors (EDs), capable of modulating the sex hormone system of an organism, can exert long-lasting negative effects on reproduction in both humans and the environment. For these reasons, the properties of EDs prevent a substance from being approved for marketing. However, regulatory tes...

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Main Authors: Steve U. Ayobahan, Julia Alvincz, Hannes Reinwald, Jannis Strompen, Gabriela Salinas, Christoph Schäfers, Elke Eilebrecht, Sebastian Eilebrecht
Format: Article
Language:English
Published: Elsevier 2023-01-01
Series:Ecotoxicology and Environmental Safety
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0147651323000180
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author Steve U. Ayobahan
Julia Alvincz
Hannes Reinwald
Jannis Strompen
Gabriela Salinas
Christoph Schäfers
Elke Eilebrecht
Sebastian Eilebrecht
author_facet Steve U. Ayobahan
Julia Alvincz
Hannes Reinwald
Jannis Strompen
Gabriela Salinas
Christoph Schäfers
Elke Eilebrecht
Sebastian Eilebrecht
author_sort Steve U. Ayobahan
collection DOAJ
description Endocrine disruptors (EDs), capable of modulating the sex hormone system of an organism, can exert long-lasting negative effects on reproduction in both humans and the environment. For these reasons, the properties of EDs prevent a substance from being approved for marketing. However, regulatory testing to evaluate endocrine disruption is time-consuming, costly, and animal-intensive. Here, we combined sublethal zebrafish embryo assays with transcriptomics and proteomics for well-characterized endocrine disrupting reference compounds to identify predictive biomarkers for sexual endocrine disruption in this model. Using RNA and protein gene expression fingerprints from two different sublethal exposure concentrations, we identified specific signatures and impaired biological processes induced by ethinylestradiol, tamoxifen, methyltestosterone and flutamide 96 h post fertilization (hpf). Our study promotes vtg1 as well as cyp19a1b, fam20cl, lhb, lpin1, nr1d1, fbp1b, and agxtb as promising biomarker candidates for identifying and differentiating estrogen and androgen receptor agonism and antagonism. Evaluation of these biomarkers for pre-regulatory zebrafish embryo-based bioassays will help identify endocrine disrupting hazards of compounds at the molecular level. Such approaches additionally provide weight-of-evidence for the identification of putative EDs and may contribute significantly to a reduction in animal testing in higher tier studies.
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spelling doaj.art-64ddbfd9418448d3844a92ab4d5611702023-01-15T04:21:05ZengElsevierEcotoxicology and Environmental Safety0147-65132023-01-01250114514Comprehensive identification of gene expression fingerprints and biomarkers of sexual endocrine disruption in zebrafish embryoSteve U. Ayobahan0Julia Alvincz1Hannes Reinwald2Jannis Strompen3Gabriela Salinas4Christoph Schäfers5Elke Eilebrecht6Sebastian Eilebrecht7Fraunhofer Attract Eco'n'OMICs, Fraunhofer Institute for Molecular Biology and Applied Ecology, Schmallenberg, GermanyFraunhofer Attract Eco'n'OMICs, Fraunhofer Institute for Molecular Biology and Applied Ecology, Schmallenberg, GermanyFraunhofer Attract Eco'n'OMICs, Fraunhofer Institute for Molecular Biology and Applied Ecology, Schmallenberg, Germany; Department Evolutionary Ecology and Environmental Toxicology, Faculty Biological Sciences, Goethe University Frankfurt, Frankfurt, GermanyFraunhofer Attract Eco'n'OMICs, Fraunhofer Institute for Molecular Biology and Applied Ecology, Schmallenberg, GermanyNGS-Services for Integrative Genomics, University of Göttingen, Göttingen, GermanyDepartment of Ecotoxicology, Fraunhofer Institute for Molecular Biology and Applied Ecology, Schmallenberg, GermanyDepartment of Ecotoxicology, Fraunhofer Institute for Molecular Biology and Applied Ecology, Schmallenberg, GermanyFraunhofer Attract Eco'n'OMICs, Fraunhofer Institute for Molecular Biology and Applied Ecology, Schmallenberg, Germany; Corresponding author.Endocrine disruptors (EDs), capable of modulating the sex hormone system of an organism, can exert long-lasting negative effects on reproduction in both humans and the environment. For these reasons, the properties of EDs prevent a substance from being approved for marketing. However, regulatory testing to evaluate endocrine disruption is time-consuming, costly, and animal-intensive. Here, we combined sublethal zebrafish embryo assays with transcriptomics and proteomics for well-characterized endocrine disrupting reference compounds to identify predictive biomarkers for sexual endocrine disruption in this model. Using RNA and protein gene expression fingerprints from two different sublethal exposure concentrations, we identified specific signatures and impaired biological processes induced by ethinylestradiol, tamoxifen, methyltestosterone and flutamide 96 h post fertilization (hpf). Our study promotes vtg1 as well as cyp19a1b, fam20cl, lhb, lpin1, nr1d1, fbp1b, and agxtb as promising biomarker candidates for identifying and differentiating estrogen and androgen receptor agonism and antagonism. Evaluation of these biomarkers for pre-regulatory zebrafish embryo-based bioassays will help identify endocrine disrupting hazards of compounds at the molecular level. Such approaches additionally provide weight-of-evidence for the identification of putative EDs and may contribute significantly to a reduction in animal testing in higher tier studies.http://www.sciencedirect.com/science/article/pii/S0147651323000180TranscriptomicsProteomicsZebrafish embryoAndrogen receptorEstrogen receptorEndocrine disruption
spellingShingle Steve U. Ayobahan
Julia Alvincz
Hannes Reinwald
Jannis Strompen
Gabriela Salinas
Christoph Schäfers
Elke Eilebrecht
Sebastian Eilebrecht
Comprehensive identification of gene expression fingerprints and biomarkers of sexual endocrine disruption in zebrafish embryo
Ecotoxicology and Environmental Safety
Transcriptomics
Proteomics
Zebrafish embryo
Androgen receptor
Estrogen receptor
Endocrine disruption
title Comprehensive identification of gene expression fingerprints and biomarkers of sexual endocrine disruption in zebrafish embryo
title_full Comprehensive identification of gene expression fingerprints and biomarkers of sexual endocrine disruption in zebrafish embryo
title_fullStr Comprehensive identification of gene expression fingerprints and biomarkers of sexual endocrine disruption in zebrafish embryo
title_full_unstemmed Comprehensive identification of gene expression fingerprints and biomarkers of sexual endocrine disruption in zebrafish embryo
title_short Comprehensive identification of gene expression fingerprints and biomarkers of sexual endocrine disruption in zebrafish embryo
title_sort comprehensive identification of gene expression fingerprints and biomarkers of sexual endocrine disruption in zebrafish embryo
topic Transcriptomics
Proteomics
Zebrafish embryo
Androgen receptor
Estrogen receptor
Endocrine disruption
url http://www.sciencedirect.com/science/article/pii/S0147651323000180
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