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

Environ Pollut. 2017 Dec;231(Pt 1):22-36. doi: 10.1016/j.envpol.2017.07.095. Epub 2017 Aug 4.


Although 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.

Keywords: Bisphenol A; Metabolic disruption; Non-targeted metabolomics; Transcriptomics; Zebrafish.

MeSH terms

  • Animals
  • Benzhydryl Compounds / toxicity*
  • Chromatography, Liquid
  • Endocrine Disruptors / toxicity*
  • Fish Proteins / chemistry
  • Fish Proteins / genetics*
  • Fish Proteins / metabolism
  • Mass Spectrometry
  • Metabolome / drug effects
  • Metabolomics / methods
  • Phenols / toxicity*
  • Transcriptome / drug effects
  • Zebrafish / genetics
  • Zebrafish / growth & development
  • Zebrafish / metabolism*


  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Fish Proteins
  • Phenols
  • bisphenol A