Perinatal exposure to low-dose DE-71 increases serum thyroid hormones and gonadal osteopontin gene expression.
Perinatal exposure to low-dose DE-71 increases serum thyroid hormones and gonadal osteopontin gene expression.
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DOI：
10.1258/ebm.2010.010334
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发表时间：
2011-04-01
期刊：
影响因子：
--
通讯作者：
LaVoie HA
中科院分区：
文献类型：
--
作者：
Blake CA;McCoy GL;Hui YY;LaVoie HA
多溴联苯醚（PBDEs）是一种广泛用于制造业的阻燃剂。它们是主要的家庭和环境污染物，具有生物累积性。人类主要通过吸入粉尘和从饮食中摄入动物产品而接触到这种物质。在动物研究中，高剂量的五溴二苯醚（五溴二苯醚）（毫克/千克体重）会对大脑发育、行为、记忆、循环甲状腺激素浓度、生殖系统和骨骼发育产生不利影响。我们调查了怀孕和哺乳期大鼠摄入相对低剂量的五溴二苯醚混合物DE-71对F1后代生殖和甲状腺参数的影响。从妊娠第1.5天至哺乳期（分娩当天除外），F0代母体每天经口灌胃给予60 μg/kg BW DE-71或溶剂。在21日龄时处死F1代幼仔，或在约80日龄时处死远交代幼仔。在妊娠第14.5天或5月龄时处死饲养的F1代雌性动物。在5月龄时处死繁殖的F1雄性。DE-71给药影响了F1代雌性动物，表现为80日龄和5个月龄时体重降低、妊娠第14.5天血清T3和T4浓度升高以及5个月龄时甲状腺重量和卵巢骨桥蛋白mRNA增加。围产期DE-71暴露也增加了21日龄F1雄性的睾丸骨桥蛋白mRNA。利用颗粒细胞体外模型，我们证明DE-71激活大鼠骨桥蛋白基因启动子。我们的研究结果是第一次证明，多溴联苯醚增加啮齿动物循环T3和T4浓度和性腺骨桥蛋白mRNA，并激活骨桥蛋白基因启动子。这些变化可能具有临床意义，因为其他人已经表明人类接触多溴二苯醚与亚临床甲状腺功能亢进症之间存在关联，卵巢骨桥蛋白的过度表达与卵巢癌有关。
Polybrominated diphenyl ethers (PBDEs) are flame retardants that have been widely used in manufacturing. They are major household and environmental contaminants that bioaccumulate. Humans are exposed primarily through dust inhalation and dietary ingestion of animal products. In animal studies, high doses of penta-brominated diphenyl ethers (penta-BDEs) in the mg/kg body weight (BW) range negatively impact brain development, behavior, memory, circulating thyroid hormone concentrations, the reproductive system and bone development. We investigated the effects of ingestion of a relatively low dose of the penta-BDE mixture DE-71 by pregnant and lactating rats on reproductive and thyroid parameters of the F1 offspring. F0 mothers received 60 μg/kg BW of DE-71 or vehicle daily by gavage from Day 1.5 of pregnancy through lactation (except the day of parturition). F1 pups were sacrificed at 21 d of age or outbred at approximately 80 d of age. Bred F1 females were sacrificed at Day 14.5 of pregnancy or at five months of age. Bred F1 males were sacrificed at five months of age. DE-71 treatment of the mothers affected the F1 females as evidenced by lower body weights at 80 d and five months of age, elevated serum T3 and T4 concentrations at Day 14.5 of pregnancy and increased thyroid gland weight and ovarian osteopontin mRNA at five months of age. Perinatal DE-71 exposure also increased testicular osteopontin mRNA in 21-day-old F1 males. Utilizing a granulosa cell in vitro model, we demonstrated that DE-71 activated the rat osteopontin gene promoter. Our results are the first to demonstrate that PBDEs increase rodent circulating T3 and T4 concentrations and gonadal osteopontin mRNA, and activate the osteopontin gene promoter. These changes may have clinical implications as others have shown associations between human exposure to PBDEs and subclinical hyperthyroidism, and overexpression of ovarian osteopontin has been associated with ovarian cancer.
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