Induction of cells differentiation and ABC transporters expression by a myco-estrogen, zearalenone, in human choriocarcinoma cell line (BeWo)

Toxicology. 2009 Sep 19;263(2-3):100-7. doi: 10.1016/j.tox.2009.06.023. Epub 2009 Jul 4.


The mycotoxin zearalenone, produced by Fusarium species, is a worldwide contaminant of concern in cereals and other plant products. Due to its estrogenic activity, zearalenone (ZEA) is known to have toxicological effect in animals on reproductive system and the placental transfer of ZEA was suggested by in vivo studies. Although passive diffusion is the principal transport mechanism across the placenta, several carrier-mediated transport protein such as ABC transporter (P-gp, MRP1, MRP2, BCRP) have been identified in the placenta. In this work, we have investigated the effect of ZEA on trophoblast differentiation and ABC transporter expression by using an in vitro model of transplacental barrier, the BeWo cell line. In the presence of 10 microM ZEA morphological (syncytium formation) and biochemical (hCG secretion) differentiation of BeWo cells were observed after a 48h exposure. Results were compared to 17beta-estradiol (E2) and an inducer of syncytialisation (forskolin). The influence of cell differentiation and ZEA exposure on expression profiles of major ABC transporters was investigated in BeWo cells: expression of mRNA MRP1, MRP2 and BCRP was induced after 24h of ZEA exposure. Induction of P-gp, MRP1, and MRP2 protein was observed after 48h of ZEA exposure. Similar results were obtained after forskolin exposure. Our study reported for the first time the implication of a food contaminant in biological effect and ABC transporter expression modulation in human choriocarcinoma cells.

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism*
  • Cell Differentiation / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Choriocarcinoma / genetics
  • Choriocarcinoma / metabolism
  • Choriocarcinoma / pathology
  • Colforsin / pharmacology
  • Coloring Agents / metabolism
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology
  • Estrogens, Non-Steroidal / pharmacology*
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Pregnancy
  • Tetrazolium Salts / metabolism
  • Thiazoles / metabolism
  • Time Factors
  • Trophoblasts / metabolism
  • Trophoblasts / physiology*
  • Zearalenone / pharmacology*


  • ATP-Binding Cassette Transporters
  • Coloring Agents
  • Drug Combinations
  • Estrogens, Non-Steroidal
  • Tetrazolium Salts
  • Thiazoles
  • Colforsin
  • Estradiol
  • Zearalenone
  • thiazolyl blue