Increased Cellular Distribution of Vimentin and Ret in the Cingulum of Rat Offspring After Developmental Exposure to Decabromodiphenyl Ether or 1,2,5,6,9,10-Hexabromocyclododecane

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  • FUJIMOTO Hitoshi
    Division of Pathology, National Institute of Health Sciences, 1–18–1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan
  • WOO Gye-Hyeong
    Division of Pathology, National Institute of Health Sciences, 1–18–1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan
  • MORITA Reiko
    Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan
  • ITAHASHI Megu
    Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan
  • AKANE Hirotoshi
    Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan
  • NISHIKAWA Akiyoshi
    Biological Safety Research Center, National Institute of Health Sciences, 1–18–1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan
  • SHIBUTANI Makoto
    Division of Pathology, National Institute of Health Sciences, 1–18–1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan

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To determine effects of developmental exposure to brominated flame retardants (BFRs), weak thyroid hormone disruptors, on white matter development, white matter-specific global gene expression analysis was performed using microdissection techniques and microarrays in male rats exposed maternally to decabromodiphenyl ether (DBDE), one of the representative BFRs, at 10, 100 or 1000 ppm. Based on previous gene expression profiles of developmental hypothyroidism and DBDE-exposed cases, vimentin+ immature astrocytes and ret proto-oncogene (Ret)+ oligodendrocytes were immunohistochemically examined after developmental exposure to representative BFRs, i.e., DBDE, 1,2,5,6,9,10-hexabromocyclododecane (HBCD; 100, 1000 or 10,000 ppm) and tetrabromobisphenol A (TBBPA; 100, 1000 or 10,000 ppm). Vimentin+ and Ret+ cell populations increased at ≥ 100 ppm and ≥ 10 ppm DBDE, respectively. Vimentin+ and Ret+ cells increased at ≥ 1000 ppm HBCD, with no effect of TBBPA. The highest dose of DBDE and HBCD revealed subtle fluctuations in serum thyroid-related hormone concentrations. Thus, DBDE and HBCD may exert direct effects on glial cell development at ≥ middle doses. At high doses, hypothyroidism may additionally be an inducing mechanism, although its contribution is rather minor.

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