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Characterization Of Toxicity Pathways Of 17β-Trenbolone in Fathead Minnows (Pimephales Promelas): Linking Molecular Key Events with Apical Outcomes

dc.contributor.advisorHecker, Markus
dc.contributor.committeeMemberBrinkmann, Markus
dc.contributor.committeeMemberHogan, Natacha
dc.contributor.committeeMemberNiyogi, Som
dc.creatorFuchylo, Ulyana
dc.date.accessioned2024-05-28T14:23:12Z
dc.date.available2024-05-28T14:23:12Z
dc.date.copyright2024
dc.date.created2024-05
dc.date.issued2024-05-28
dc.date.submittedMay 2024
dc.date.updated2024-05-28T14:23:12Z
dc.description.abstract17β-Trenbolone (TRB) is an anabolic steroid that is used as a growth promoter in the beef cattle industry and has been found in nearby water bodies. Due to its function as an androgen receptor (AR) agonist, it has been found to have a masculinizing effect on female fish. This has become an issue of concern as any non-target organisms that come into contact with TRB through run-off can be adversely impacted. This unintended exposure can eventually have population-level impacts. The objective of this study was to expose female fathead minnows to TRB for 21 d and identify any connections between impacts of exposure seen after 4 d at the molecular level (transcriptomics) and those seen at the end of the exposure period at the apical level. The goal of exploring this connection between molecular and apical outcomes of exposure was to determine if and which genes could possibly be used to explain and predict the effects seen at the apical level. Transcriptomics data were generated from livers and gonads collected from female fish exposed to 0.01% dimethyl sulfoxide (v/v) (solvent control), 9.5 ng/L and 81 ng/L TRB treatment groups. Enrichment analyses did not find any significant GO terms in neither the livers nor gonads. Over representation analyses (ORA) did, however, find two significantly dysregulated GO terms in the high treatment group gonads. These were related to the nuclear pore (cellular component; adjusted P-value<0.05) and the structural constituent of the nuclear pore (molecular function; adjusted P-value<0.005). In general, significantly dysregulated genes in both the gonads and livers were involved in general cellular processes such as protein binding and transport, and cytoskeletal structure and organization. While molecular results did not show the expected effects on the reproductive system, apical results did. Fecundity in the high treatment group was significantly lower than all other treatment groups as egg production halted within 16 d of exposure. Furthermore, histopathology showed a disruption in yolk accumulation in the oocytes of the high treatment group females, indicating a potential disruption of vitellogenesis. These results suggest that the low concentrations used in this study likely resulted in impacts on gene expression related to TRB’s function as an anabolic steroid, as opposed to those impacts commonly reported at higher concentrations. Nonetheless, these low concentrations are able to cause a decline in reproduction, as there was clearly an adverse impact on fecundity.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/10388/15713
dc.language.isoen
dc.subjecttrenbolone
dc.subjecttranscriptomics
dc.subjectgene expression
dc.subjectfathead minnows
dc.titleCharacterization Of Toxicity Pathways Of 17β-Trenbolone in Fathead Minnows (Pimephales Promelas): Linking Molecular Key Events with Apical Outcomes
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentToxicology Centre
thesis.degree.disciplineToxicology
thesis.degree.grantorUniversity of Saskatchewan
thesis.degree.levelMasters
thesis.degree.nameMaster of Science (M.Sc.)

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