Quantitative Proteomic Investigation of Estrogenic Endocrine-Disrupting Effects in the Rat Uterus

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dc.contributor.advisorProkai, Laszlo
dc.contributor.committeeMemberLacko, Andras G.
dc.contributor.committeeMemberBorejdo, Julian
dc.creatorRahlouni, Fatima R.
dc.date.accessioned2019-08-22T21:05:32Z
dc.date.available2019-08-22T21:05:32Z
dc.date.issued2016-05-01
dc.date.submitted2016-08-05T09:06:06-07:00
dc.description.abstractThe mammalian uterus is one of the most sensitive organs for estrogenicity. However, the widely used rat uterotrophic assay to assess known and potential estrogenic compounds only considers the uterine wet weight gain as an endpoint measurement. To complement this method with an advanced technology that reveals molecular targets, we analyzed changes in protein expression using label-free quantitative proteomic analysis by liquid chromatography–mass spectrometry from uterine protein extracts of ovariectomized rats after daily 17β-estradiol exposure for five days. We performed shotgun proteomic analysis of the uterus to identify candidate proteins for use as markers of estrogenicity. In addition, we mapped the differentially expressed proteins from untargeted analysis to signaling networks and biological processes through Ingenuity Pathway Analysis. We selected twelve of the top up- and down-regulated proteins for further evaluation by selected reaction monitoring-based targeted quantitation. Of the final six candidate markers, we verified all six as markers of estrogenicity by the application of the panel to testing rats exposed to a low and high dose of the known estrogenic compound bisphenol A. Altogether, the results of this study demonstrate the power of combining untargeted and targeted quantitative proteomic methods for a comprehensive analysis in rat uterus to evaluate changes in protein expression levels due to estrogen exposure, and to uncover candidate markers of estrogenicity in the development of a targeted proteomics panel.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/29061
dc.language.isoen
dc.provenance.legacyDownloads42
dc.subjectMedical Sciences
dc.subjectMedicine and Health Sciences
dc.subjectestrogen
dc.subjectquantitative proteomics
dc.subjectrat
dc.subjectuterus
dc.titleQuantitative Proteomic Investigation of Estrogenic Endocrine-Disrupting Effects in the Rat Uterus
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplineBiomedical Sciences
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

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