Metabolism disruption analysis of zebrafish larvae in response to BPA and BPA analogs based on RNA-Seq technique

Ecotoxicol Environ Saf. 2019 Jun 15;174:181-188. doi: 10.1016/j.ecoenv.2019.01.126. Epub 2019 Feb 28.


Bisphenol A (BPA) is an environmentally ubiquitous chemical widely used in industry and is known to have adverse effects on organisms. Given the negative effect, BPA-free products have been developed with BPA analogs such as bisphenol F (BPF) and bisphenol S (BPS); however, these analogs are proving to exhibit toxicity similar to that of BPA. In the present study, we aimed to identify and compare the underlying mechanisms of toxicity of BPA, BPF, and BPS at the transcriptional level by conducting global transcriptome sequencing (RNA-Seq) on zebrafish embryos. RNA-seq results showed that the expression levels of 285, 191, and 246 genes were significantly changed in zebrafish larvae after embryos were treated for 120 h with 100 μg/L BPA, BPF, and BPS, respectively. Among the genes exhibiting altered expression, a substantial number were common to two or three exposure groups, suggesting consistent toxicity between the three bisphenols. We further validated the expression levels of 19 differentially expressed genes by qRT-PCR, using sequencing RNA and the RNA samples after treatment by 0.01, 1, and 100 μg/L bisphenols under identical condition, the results were similar to RNA-Seq. Moreover, functional enrichment analysis indicated that metabolism was the main pathway which disrupted in zebrafish larvae by bisphenols treatment. Protein-protein interaction network analysis indicated that six DEGs (ces, cda, dpyd, upp1, upp2, and cmpk2) interact together in the drug metabolism of zebrafish. In summary, our study revealed changes in the transcription of genes upon bisphenols treatment in zebrafish larvae for the first time, indicating that BPF and BPS may cause adverse effects similar to BPA via their involvement in various biological processes, providing a solid foundation for further research on the toxicology of BPA analogs.

Keywords: Bisphenol A; Bisphenol F; Bisphenol S; Metabolism; RNA sequencing; Zebrafish embryos.

MeSH terms

  • Animals
  • Benzhydryl Compounds / toxicity*
  • Dose-Response Relationship, Drug
  • Embryo, Nonmammalian / drug effects*
  • Embryo, Nonmammalian / metabolism
  • Gene Expression Profiling
  • Larva
  • Phenols / toxicity*
  • RNA / genetics
  • Sequence Analysis, RNA
  • Sulfones / toxicity*
  • Transcriptome / drug effects
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish / metabolism*


  • Benzhydryl Compounds
  • Phenols
  • Sulfones
  • bisphenol F
  • RNA
  • bis(4-hydroxyphenyl)sulfone
  • bisphenol A