Toxic effects of bisphenol A diglycidyl ether and derivatives in human placental cells

Environ Pollut. 2019 Jan;244:513-521. doi: 10.1016/j.envpol.2018.10.045. Epub 2018 Oct 12.

Abstract

BADGE (bisphenol A diglycidyl ether) is a synthesis product of bisphenol A (BPA), which, like other plasticizers, can cross the human placenta and reach the foetus. However, compared to BPA, there is almost no toxicological information. This work investigates the toxicity, endocrine and lipid disruption potential of BADGE and its hydrolysed and chlorinated derivatives (BADGE·H2O and BADGE·2HCl) in human placental JEG-3 cells. The analysis of culture medium by HPLC-ESI(+)-QqQ evidenced a good bioavailability of BADGE·2HCl and BADGE·H2O, but low stability of BADGE. Regardless, BADGE·2HCl and BADGE showed higher cytotoxicity than BADGE·H2O, which was the only compound that significantly inhibited CYP19 activity (IC50 49 ± 5 μM). JEG-3 cells lipidome analyzed by FIA-ESI(+/-)-Orbitrap was significantly altered by exposure to BADGE·2HCl and BADGE at concentrations at the low μM range. BADGE·2HCl lead to a strong decrease of diacyl- and triacyl-glycerides (DGs,TGs) together with some membrane lipids, while BADGE lead to an accumulation of TGs. The results evidence the ability of BADGE and derivatives to affect placental lipid handling and to modulate placental CYP19 activity (BADGE·H2O) and highlights the need to monitor human exposure to these compounds, at least as intensely as BPA is monitored.

Keywords: Bisphenol A diglycidyl ether; CYP19; Cytotoxicity; JEG-3 cells; Lipidome.

MeSH terms

  • Aromatase / metabolism*
  • Aromatase Inhibitors / toxicity*
  • Benzhydryl Compounds / toxicity*
  • Carcinogens / toxicity*
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid / methods
  • Diglycerides / metabolism
  • Epoxy Compounds / toxicity*
  • Female
  • Humans
  • Membrane Lipids / metabolism
  • Phenols / toxicity*
  • Placenta / cytology*
  • Placenta / drug effects
  • Plasticizers / toxicity*
  • Pregnancy
  • Reactive Oxygen Species / metabolism
  • Triglycerides / metabolism

Substances

  • Aromatase Inhibitors
  • Benzhydryl Compounds
  • Carcinogens
  • Diglycerides
  • Epoxy Compounds
  • Membrane Lipids
  • Phenols
  • Plasticizers
  • Reactive Oxygen Species
  • Triglycerides
  • Aromatase
  • CYP19A1 protein, human
  • 2,2-bis(4-glycidyloxyphenyl)propane
  • bisphenol A