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Metabolic disruption of zebrafish (Danio rerio) embryos by bisphenol A. An integrated metabolomic and transcriptomic approach

AuthorsOrtiz-Villanueva, Elena; Navarro-Martín, Laia ; Jaumot, Joaquim ; Benavente, Fernando; Sanz-Nebot, Victoria M.; Piña, Benjamín ; Tauler, Romà
KeywordsBisphenol A
Metabolic disruption
Non-targeted metabolomics
Issue Date2017
CitationEnvironmental Pollution: 231: 22-36 (2017)
AbstractAlthough bisphenol A (BPA) is commonly recognized as an endocrine disruptor, the metabolic consequences of its exposure are still poorly understood. In this study, we present a non-targeted LC-MS based metabolomic analysis in combination with a full-genome, high-throughput RNA sequencing (RNA-Seq) to reveal the metabolic effects and the subjacent regulatory pathways of exposing zebrafish embryos to BPA during the first 120 hours post-fertilization. We applied multivariate data analysis methods to extract biochemical information from the LC-MS and RNA-Seq complex datasets and to perform testable predictions of the phenotypic adverse effects. Metabolomic and transcriptomic data revealed a similar subset of altered pathways, despite the large difference in the number of identified biomarkers (around 50 metabolites and more than 1000 genes). These results suggest that even a moderate coverage of zebrafish metabolome may be representative of the global metabolic changes. These multi-omic responses indicate a specific metabolic disruption by BPA affecting different signaling pathways, such as retinoid and prostaglandin metabolism. The combination of transcriptomic and metabolomic data allowed a dynamic interpretation of the results that could not be drawn from either single dataset. These results illustrate the utility of -omic integrative analyses for characterizing the physiological effects of toxicants beyond the mere indication of the affected pathways. © 2017 Elsevier Ltd
Publisher version (URL)https://doi.org/10.1016/j.envpol.2017.07.095
Appears in Collections:(IDAEA) Artículos
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