Application of omic approaches on the mechanisms of pollutants using Daphnia magna as model species
[eng] Environmental toxicology is undergoing a paradigm shift due to the new concerning environmental reality. Nowadays, to manage subtler and chronic effects of chemicals, either single or mixtures, is an imperative need, especially at low and environmentally relevant concentrations. Not least impo...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/175284 |
| Acceso en línea: | https://hdl.handle.net/2445/175284 http://hdl.handle.net/10803/671146 |
| Access Level: | acceso abierto |
| Palabra clave: | Toxicologia ambiental Metabolòmica Transcripció genètica Lípids Cladòcers Environmental toxicology Metabolomics Genetic transcription Lipids Cladocera |
| Sumario: | [eng] Environmental toxicology is undergoing a paradigm shift due to the new concerning environmental reality. Nowadays, to manage subtler and chronic effects of chemicals, either single or mixtures, is an imperative need, especially at low and environmentally relevant concentrations. Not least important is to deal with emerging contaminants (ECs), whose harmful effects in ecosystems and toxicity mechanisms are still unknown. Therefore, new strategies for assessing the toxicity of pollutants with greater environmental relevance must be developed, what requires the application of integrative approaches combining tools from different disciplines. Omic technologies allow the holistic measurement of effects at low levels of biological organization in high throughput platforms, and provide mechanistic data which may become essential in the development and application of more efficient and effective testing strategies. Overall, this thesis aimed to prove the importance of integrating omic and conventional toxicological approaches in order to obtain significant information that helps to unravel any new toxicity mechanism triggered by ECs on the aquatic environment using Daphnia magna as model species. The ECs studied included suspected lipid disruptors (endocrine disrupting compounds, EDCs) and ECs that are known to affect the central nervous system (i.e. neuroactive pharmaceuticals and other chemicals). Different integrative approaches have been developed to assess the toxicity of these compounds by linking effects on reproduction and behavior (individual organism responses), with gene expression changes and its subsequent metabolomic (and thus lipidomic) disruption in D. magna. The ability of EDCs and neuroactive pharmaceuticals to affect reproduction and disrupt lipid homeostasis, as well as the molecular signaling pathways that modulate this disruption, has been addressed throughout the thesis. Within the chapter 2, microarray transcriptomic analysis of D. magna adult females exposed to some EDCs during reproduction was performed, together with the effects on their lipidome by a lipidomic analysis using UHPLC-TOF MS. Common transcriptional mechanisms were identified as energy-related categories, molting and reproduction, and different lipid functional categories. The obtained results allowed to link reproductive effects with changes in lipid profiles and disrupted transference of lipids to eggs in D. magna females. Lipidomic effects of neuroactive pharmaceuticals at environmental concentrations and the driven molecular mechanisms behind them were studied in chapter 3. The hypothesis that serotonin may be involved in regulating lipid dynamics and fecundity responses in D. magna was confirmed by the analysis of the lipidome of genetically tryptophan hydrolase gene knockout clones. Finally, in chapter 4 a targeted metabolomic approached was developed to analyze neurotransmitters in D. magna samples and employed in the study of the effects of neuroactive pharmaceuticals that affected Daphnias’ cognitive behavior. Metabolomic results were linked to the associated transcriptional disruption studied through RNAseq, probing the suitability of these organisms for environmental neurotoxicity studies. Overall, the results obtained throughout this thesis allowed to link transcriptomic signaling pathways with metabolomic effects (lipidomic and neurotransmitter profiles) and with apical responses (reproduction and behavior). |
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