Developmental exposure of decabromodiphenyl ether impairs subventricular zone neurogenesis and morphology of granule cells in mouse olfactory bulb

Arch Toxicol. 2018 Jan;92(1):529-539. doi: 10.1007/s00204-017-2059-x. Epub 2017 Sep 7.

Abstract

Polybrominated diphenyl ethers (PBDEs) are additive flame retardants widely used in various products (e.g., textiles, consumer electronics, and plastics). Strong evidence indicates that PBDEs are developmental neurotoxicants that can cause neurodevelopmental disabilities and cognitive defects. Currently, decabromodiphenyl ether (BDE 209) is the only PBDE permitted for production in most countries. This study investigated the impact of BDE 209 on postnatal neurogenesis in the subventricular zone (SVZ) of ICR mice. For this purpose, pregnant ICR mice were orally administrated a daily dose of 0, 20 or 100 mg/kg BDE 209 from gestation day 6 to postnatal day 16. Bromodeoxyuridine (BrdU) incorporation and in vivo postnatal electroporation were performed to label the newly generated cells in the SVZ. On PND 16, a reduction of type-B stem cells was found in the 100 mg/kg group. BDE 209 also decreased the number of newborn cells and Calretinin+ interneurons in granule cell layer at the dose of 100 mg/kg. In addition, we observed impaired neuronal migration and dendritic development of newborn olfactory granule cells in both 20 and 100 mg/kg groups. In conclusion, developmental exposure to BDE 209 produces adverse effects on SVZ neurogenesis and dendritic growth of mouse offspring. These findings suggest a potential risk of BDE 209 in human neurodevelopment.

Keywords: Decabromodiphenyl ether; Interneurons; Morphology; Neurogenesis; Olfactory bulb; Subventricular zone.

MeSH terms

  • Animals
  • Animals, Newborn
  • Calreticulin / metabolism
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Dendrites / drug effects
  • Dendrites / pathology
  • Female
  • Flame Retardants / toxicity
  • Halogenated Diphenyl Ethers / toxicity*
  • Lateral Ventricles / drug effects*
  • Lateral Ventricles / pathology
  • Male
  • Mice, Inbred ICR
  • Neurogenesis / drug effects
  • Olfactory Bulb / drug effects*
  • Olfactory Bulb / pathology
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Stem Cells / drug effects
  • Stem Cells / pathology

Substances

  • Calreticulin
  • Flame Retardants
  • Halogenated Diphenyl Ethers
  • decabromobiphenyl ether