title: Polybrominated diphenyl ethers induce developmental neurotoxicity in a human in vitro model: evidence for endocrine disruption.
abstract: BACKGROUND
  Polybrominated diphenyl ethers (PBDEs) are persistent and bioaccumulative flame retardants, which are found in rising concentrations in human tissues. They are of concern for human health because animal studies have shown that they possess the potential to be developmentally neurotoxic.
  
  
  OBJECTIVE
  Because there is little knowledge of the effects of PBDEs on human brain cells, we investigated their toxic potential for human neural development in vitro. Moreover, we studied the involvement of thyroid hormone (TH) disruption in the effects caused by PBDEs.
  
  
  METHODS
  We used the two PBDE congeners BDE-47 and BDE-99 (0.1-10 microM), which are most prominent in human tissues. As a model of neural development, we employed primary fetal human neural progenitor cells (hNPCs), which are cultured as neurospheres and mimic basic processes of brain development in vitro: proliferation, migration, and differentiation.
  
  
  RESULTS
  PBDEs do not disturb hNPC proliferation but decrease migration distance of hNPCs. Moreover, they cause a reduction of differentiation into neurons and oligodendrocytes. Simultaneous exposure with the TH receptor (THR) agonist triiodothyronine rescues these effects on migration and differentiation, whereas the THR antagonist NH-3 does not exert an additive effect.
  
  
  CONCLUSIONS
  PBDEs disturb development of hNPCs in vitro via endocrine disruption of cellular TH signaling at concentrations that might be of relevance for human exposure.
authors.affiliation: Group of Toxicology, Institut für umweltmedizinische Forschung gGmbH an der Heinrich Heine-Universität, Düsseldorf, Germany.
authors.forename: Timm
authors.initials: T
authors.lastname: Schreiber
authors.forename: Kathrin
authors.initials: K
authors.lastname: Gassmann
authors.forename: Christine
authors.initials: C
authors.lastname: Götz
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hübenthal
authors.forename: Michaela
authors.initials: M
authors.lastname: Moors
authors.forename: Guido
authors.initials: G
authors.lastname: Krause
authors.forename: Hans F
authors.initials: HF
authors.lastname: Merk
authors.forename: Ngoc-Ha
authors.initials: NH
authors.lastname: Nguyen
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Scanlan
authors.forename: Josef
authors.initials: J
authors.lastname: Abel
authors.forename: Christine R
authors.initials: CR
authors.lastname: Rose
authors.forename: Ellen
authors.initials: E
authors.lastname: Fritsche
mesh_terms: D001921:Brain / Q000166:cytology* / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005411:Flame Retardants / Q000633:toxicity; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D006801:Humans; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects
chemical_list: D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers