Proteomics Complementation of the Rat Uterotrophic Assay for Estrogenic Endocrine Disruptors: A Roadmap of Advancing High Resolution Mass Spectrometry-Based Shotgun Survey to Targeted Biomarker Quantifications

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dc.creatorProkai, Laszlo
dc.creatorRahlouni, Fatima
dc.creatorZaman, Khadiza
dc.creatorNguyen, Vien
dc.creatorProkai-Tatrai, Katalin
dc.creator.orcid0000-0002-4559-3458 (Prokai, Laszlo)
dc.creator.orcid0000-0001-5595-1346 (Prokai-Tatrai, Katalin)
dc.date.accessioned2022-11-17T21:59:24Z
dc.date.available2022-11-17T21:59:24Z
dc.date.issued2021-02-08
dc.description.abstractThe widely used rat uterotrophic assay to assess known and potential estrogenic compounds only considers uterine weight gain as endpoint measurement. To complement this method with an advanced technology that reveals molecular targets, we analyzed changes in protein expression using label-free quantitative proteomics by nanoflow liquid chromatography coupled with high-resolution mass spectrometry and tandem mass spectrometry from uterine protein extracts of ovariectomized rats after daily 17beta-estradiol exposure for five days in comparison with those of vehicle-treated control animals. Our discovery-driven study revealed 165 uterine proteins significantly regulated by estrogen treatment and mapped by pathway analyses. Estrogen-regulated proteins represented cell death, survival and development, cellular growth and proliferation, and protein synthesis as top molecular and cellular functions, and a network found with the presence of nuclear estrogen receptor(s) as a prominent molecular node confirmed the relevance of our findings to hormone-associated events. An exploratory application of targeted proteomics to bisphenol A as a well-known example of an estrogenic endocrine disruptor is also presented. Overall, the results of this study have demonstrated the power of combining untargeted and targeted quantitative proteomic strategies to identify and verify candidate molecular markers for the evaluation of endocrine-disrupting chemicals to complement a conventional bioassay.
dc.description.sponsorshipThis research was funded by The Welch Foundation (endowment BK-0031 to L.P.), the National Institutes of Health (grants AG031535 to L.P., and EY027005 to K.P.-T.) and a predoctoral bridge funding by the Graduate School of Biomedical Sciences at the University of North Texas Health Science Center (to F.R.).
dc.identifier.citationProkai, L., Rahlouni, F., Zaman, K., Nguyen, V., & Prokai-Tatrai, K. (2021). Proteomics Complementation of the Rat Uterotrophic Assay for Estrogenic Endocrine Disruptors: A Roadmap of Advancing High Resolution Mass Spectrometry-Based Shotgun Survey to Targeted Biomarker Quantifications. International journal of molecular sciences, 22(4), 1686. https://doi.org/10.3390/ijms22041686
dc.identifier.issn1422-0067
dc.identifier.issue4
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31936
dc.identifier.volume22
dc.publisherMDPI
dc.relation.urihttps://doi.org/10.3390/ijms22041686
dc.rights.holder© 2021 by the authors.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceInternational Journal of Molecular Sciences
dc.subject17beta-estradiol
dc.subjectbisphenol A
dc.subjectendocrine disruption
dc.subjectestrogen-regulated proteins
dc.subjecthigh resolution mass spectrometry
dc.subjectlabel-free proteomics
dc.subjectliquid chromatography-mass spectrometry
dc.subjectprotein networks
dc.subjectrat uterus
dc.subjecttargeted proteomics
dc.subject.meshAnimals
dc.subject.meshBiological Assay / methods
dc.subject.meshBiomarkers / analysis
dc.subject.meshBiomarkers / metabolism
dc.subject.meshChromatography, Liquid / methods
dc.subject.meshEndocrine Disruptors / pharmacology
dc.subject.meshFemale
dc.subject.meshGene Expression Regulation / drug effects
dc.subject.meshProteome / analysis
dc.subject.meshRats
dc.subject.meshRats, Sprague-Dawley
dc.subject.meshTandem Mass Spectrometry / methods
dc.subject.meshUterus / drug effects
dc.subject.meshUterus / metabolism
dc.titleProteomics Complementation of the Rat Uterotrophic Assay for Estrogenic Endocrine Disruptors: A Roadmap of Advancing High Resolution Mass Spectrometry-Based Shotgun Survey to Targeted Biomarker Quantifications
dc.typeArticle
dc.type.materialtext

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