thesis

Transcriptomic approaches to study the effects of xenobiotics in ruminants

Abstract

This thesis is concerned with the study and characterization of the xenobiotics-induced transcriptomic signature in some ruminants. Based on the different studies presented in this thesis, the microarray-based transcriptomics approach was able to provide a holistic view on the global gene expression in diverse types of tissues – namely, skeletal muscle, liver, whole blood, primary hepatocytes- and kidney-derived cell lines. The pre-designed commercial bovine microarray enabled the discovery of many biomarkers with which the differentiation between illicitly-treated and untreated veal calves was possible. It also demonstrated the transcriptomic signature dissimilarity between 2 tissues (i.e. skeletal muscle and liver) exposed to the same treatment (i.e. anabolic steroids). Also, the same approach revealed the presence of some transcriptomic landscape convergence between the hepatocytes primary cultures and the Madin-Darby bovine kidney (MDBK) cell line, which in turn spots the light on the MDBK cells as a possible surrogate in vitro tool for some liver-based functional studies. Finally, a custom-designed whole-transcriptome sheep (Ovis aries) microarray revealed the immune-system-induction and the transcriptional-modulation capacity of organic selenium in sheep. Collectively, the transcriptomics approach overcame the shortcoming of focusing on changes in expression of a priori list of selected genes – instead, it looks at the bigger picture within the protein-coding part of the genome. It is important to mention that using an alternative functional analysis tools [i.e. Gene set enrichment analysis (GSEA)] was useful to cross-validate the output of the conventional overrepresentation tools like the Database for Annotation, Visualization and Integrated Discovery (DAVID). The collective body of work represented here shows the adequacy of using microarray, commercial and custom-designed, to depict a holistic picture about the global gene expression profile of a given tissue. Still, there are some challenges in data analysis, interpretation and integration with the output of other alternative omic techniques – those challenges are highlighted and discussed across the different chapters of this thesis

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