Impaired oligodendroglial development by decabromodiphenyl ether in rat offspring after maternal exposure from mid-gestation through lactation

Impaired oligodendroglial development by decabromodiphenyl ether in rat offspring after maternal exposure from mid-gestation through lactation
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DOI:
10.1016/j.reprotox.2010.09.003
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发表时间:
2011-01-01
影响因子:
3.3
通讯作者:
Shibutani, Makoto
Shibutani, Makoto
中科院分区:
医学4区
文献类型:
--
作者:
Fujimoto, Hitoshi;Woo, Gye-Hyeong;Shibutani, Makoto

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从妊娠第10天(GD)至分娩后第20天(PND 20),向妊娠Sprague-Dawley大鼠喂食含有百万分之0、10、100或1000十溴二苯醚的饲料。未观察到母体和后代生殖参数的显著变化。在PND 20时,在1000 ppm(对照值的84.2%)下检查的雄性血清三碘甲状腺原氨酸浓度略微降低,两种性别的甲状腺滤泡细胞肥大发生率增加,1000 ppm下雄性存在显著差异。在两种性别动物中均观察到弥漫性肝细胞肥大伴相对肝脏重量增加和肾近端小管细胞质嗜酸性粒细胞增多,雄性和雌性动物分别与10 ppm存在显著差异。在出生后第11周,在1000 ppm(对照值的85.9%)时检查的雄性血清甲状腺素浓度略有降低,雄性甲状腺滤泡细胞肥大的发生率从10 ppm开始无显著性增加。从100 ppm开始,雄性扣带深层皮质中胼胝体面积和2 ',3'-环核苷酸3 '-磷酸二酯酶免疫反应性少突胶质细胞密度减少。相反,NeuN免疫反应神经元分布在海马CA 1区是不变的。这表明,从100 ppm开始,发育中的十溴二苯醚接触会导致针对少突胶质细胞的不可逆的白色物质发育不全,并伴有发育中的甲状腺功能减退。经确定,十溴二苯醚的最低观测不良影响水平为百万分之10(0.7-2.4毫克/千克体重-天)。(C)2010年爱思唯尔公司All rights reserved.
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). (C) 2010 Elsevier Inc. All rights reserved.