Polybrominated diphenyl ethers induce developmental neurotoxicity in a human in vitro model: Evidence for endocrine disruption

Timm Schreiber, Kathrin Gassmann, Christine Götz, Ulrike Hübenthal, Michaela Moors, Guido Krause, Hans F. Merk, Ngoc Ha Nguyen, Thomas S. Scanlan, Josef Abel, Christine R. Rose, Ellen Fritsche

Research output: Contribution to journalArticle

135 Scopus citations

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 μM), 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. Conclusion: PBDEs disturb development of hNPCs in vitro via endocrine disruption of cellular TH signaling at concentrations that might be of relevance for human exposure.

Original languageEnglish (US)
Pages (from-to)572-578
Number of pages7
JournalEnvironmental health perspectives
Volume118
Issue number4
DOIs
StatePublished - Apr 1 2010

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Keywords

  • Brain
  • Development
  • Human
  • In vitro
  • Neural
  • Neural progenitor cells
  • Neurosphere
  • PBDE
  • Toxicology

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Cite this

Schreiber, T., Gassmann, K., Götz, C., Hübenthal, U., Moors, M., Krause, G., Merk, H. F., Nguyen, N. H., Scanlan, T. S., Abel, J., Rose, C. R., & Fritsche, E. (2010). Polybrominated diphenyl ethers induce developmental neurotoxicity in a human in vitro model: Evidence for endocrine disruption. Environmental health perspectives, 118(4), 572-578. https://doi.org/10.1289/ehp.0901435