Developmental neurotoxicity of low concentrations of bisphenol A and S exposure in zebrafish

Chemosphere. 2021 Jan;262:128045. doi: 10.1016/j.chemosphere.2020.128045. Epub 2020 Aug 23.


The vulnerability to environmental insults is heightened at early stages of development. However, the neurotoxic potential of bisphenol A (BPA) and bisphenol S (BPS) at developmental windows remains unclear. To investigate the mechanisms mediating the developmental neurotoxicity, zebrafish embryos were treated with 0.01, 0.03, 0.01, 0.3, 1 μM BPA/BPS. Also, we used Tg(HuC:GFP) zebrafish to investigate whether BPA/BPS could induce neuron development. The reduction in body length, and increased heart rate were significant in 0.3 and 1 μM BPA/BPS groups. The green fluorescence protein (GFP) intensity increased at 72 hpf and 120 hpf in Tg(HuC:GFP) larvae which was consistent with the increased mRNA expression of elval3 following BPS treatments, an indication of the plausible effect of BPS on embryonic neuron development. Additionally, BPA/BPS treatments elicited hyperactivity and reduced static time in zebrafish larvae, suggesting behavioral alterations. Moreover, qRT-PCR results showed that BPA and BPS could interfere with the normal expression of development-related genes vegfa, wnt8a, and mstn1 at the developmental stages. The expression of neurodevelopment-related genes (ngn1, elavl3, gfap, α1-tubulin, mbp, and gap43) were significantly upregulated in BPA and BPS treatments, except for the remarkable downregulation of mbp and gfap elicited by BPA at 48 (0.03 μM) and 120 hpf (0.3 μM) respectively; ngn1 at 48 hpf for 0.1 μM BPS. Overall, our results highlighted that embryonic exposure to low concentrations of BPA/BPS could be deleterious to the central nervous system development and elicit behavioral abnormalities in zebrafish at developmental stages.

Keywords: Bisphenol A; Bisphenol S; Developmental effect; Neurotoxicity; Zebrafish.

MeSH terms

  • Animals
  • Benzhydryl Compounds / toxicity*
  • Embryo, Nonmammalian / drug effects*
  • Embryo, Nonmammalian / metabolism
  • Embryonic Development / drug effects*
  • Larva / drug effects
  • Larva / metabolism
  • Neurogenesis / drug effects*
  • Phenols / toxicity*
  • Sulfones / toxicity*
  • Water Pollutants, Chemical / toxicity*
  • Zebrafish Proteins / metabolism
  • Zebrafish* / metabolism


  • Benzhydryl Compounds
  • Phenols
  • Sulfones
  • Water Pollutants, Chemical
  • Zebrafish Proteins
  • bis(4-hydroxyphenyl)sulfone
  • bisphenol A