Polybrominated diphenyl ethers induce developmental neurotoxicity in a human in vitro model: evidence for endocrine disruption.
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.
Schreiber
Timm
T
Group of Toxicology, Institut für umweltmedizinische Forschung gGmbH an der Heinrich Heine-Universität, Düsseldorf, Germany.
Gassmann
Kathrin
K
Götz
Christine
C
Hübenthal
Ulrike
U
Moors
Michaela
M
Krause
Guido
G
Merk
Hans F
HF
Nguyen
Ngoc-Ha
NH
Scanlan
Thomas S
TS
Abel
Josef
J
Rose
Christine R
CR
Fritsche
Ellen
E
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
D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers