Impaired oligodendroglial development by decabromodiphenyl ether in rat offspring after maternal exposure from mid-gestation through lactation.
Pregnant Sprague-Dawley rats were given diet containing decabromodiphenyl ether (DBDE) either at 0, 10, 100, or 1000 ppm from gestation day (GD) 10 until day 20 after delivery (PND 20). No significant alterations were observed in maternal and offspring reproductive parameters. At PND 20, serum triiodothyronine concentrations examined in males were slightly reduced at 1000 ppm (84.2% of the control value), and incidence of thyroid follicular cell hypertrophy was increased in both sexes with significant difference in males at 1000 ppm. Diffuse liver cell hypertrophy accompanying increased relative liver weight and increased cytoplasmic eosinophilia of the renal proximal tubules were observed in both sexes with significant difference from 10 ppm in males and females, respectively. At postnatal week 11, serum thyroxine concentrations examined in males were slightly reduced at 1000 ppm (85.9% of the control value), and the incidence of thyroid follicular cell hypertrophy was non-significantly increased from 10 ppm in males. There were reductions in the corpus callosum area and density of 2',3'-cyclic nucleotide 3'-phosphodiesterase-immunoreactive oligodendrocytes in the cingulate deep cortex in males from 100 ppm. Conversely, NeuN-immunoreactive neuronal distribution in the hippocampal CA1 was unchanged. This suggests that developmental DBDE-exposure caused irreversible white matter hypoplasia targeting oligodendrocytes from 100 ppm, accompanied with developmental hypothyroidism. The lowest-observed-adverse-effect level of DBDE was determined to be 10 ppm (0.7-2.4 mg/kg-body weight-d).
Fujimoto
Hitoshi
H
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Woo
Gye-Hyeong
GH
Inoue
Kaoru
K
Takahashi
Miwa
M
Hirose
Masao
M
Nishikawa
Akiyoshi
A
Shibutani
Makoto
M
D000284:Administration, Oral; D000821:Animal Feed; D000818:Animals; D003337:Corpus Callosum / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D004032:Diet; D004622:Embryo, Mammalian / Q000187:drug effects / Q000196:embryology; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D005411:Flame Retardants / Q000633:toxicity*; D006179:Gyrus Cinguli / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D007774:Lactation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D018811:Maternal Exposure / Q000009:adverse effects*; D009836:Oligodendroglia / Q000187:drug effects* / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013963:Thyroid Hormones / Q000097:blood
D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D013963:Thyroid Hormones; C010902:decabromobiphenyl ether