Sex and dose-dependent effects of developmental exposure to bisphenol A on anxiety and spatial learning in deer mice (Peromyscus maniculatus bairdii) offspring.
Sex and dose-dependent effects of developmental exposure to bisphenol A on anxiety and spatial learning in deer mice (Peromyscus maniculatus bairdii) offspring.
复制标题
DOI：
10.1016/j.yhbeh.2012.09.009
复制
发表时间：
2013-01
影响因子：
3.5
通讯作者：
Rosenfeld, Cheryl S.
中科院分区：
文献类型：
--
作者：
Jasarevic, Eldin;Williams, Scott A.;Vandas, Gregory M.;Ellersieck, Mark R.;Liao, Chunyang;Kannan, Kurunthachalam;Roberts, R. Michael;Geary, David C.;Rosenfeld, Cheryl S.
关键词：
双酚A（BPA）是一种广泛生产的内分泌干扰化合物，在环境中普遍存在。数据表明，在大脑性别分化期间暴露于BPA的发育会导致后代的行为后果。远交系鹿小鼠（Peromyscus maniculatus bairdii）是此类研究的极好动物模型，因为它们表现出明确的性别和类固醇依赖行为。在这里，妊娠期和哺乳期的母鼠喂食不含植物雌激素的对照饮食，相同的饮食补充有炔雌醇（0.1ppb）或三种剂量的BPA（50 mg，5 mg，50 μg/kg饲料重量）之一。断奶后，幼鼠保持对照饮食，直到它们达到性成熟，然后评估空间学习能力和焦虑样和探索行为。相对于对照组，男性暴露于两个上限，但不是最低剂量的BPA表现出类似的空间学习障碍，增加焦虑和减少探索行为的乙炔雌二醇暴露的男性，而女性暴露于乙炔雌二醇，但不是BPA，表现出男性化的空间能力。我们还确定了长期维持较高剂量BPA的母鼠血液中是否含有与环境相关的BPA浓度。虽然对照组中未结合BPA的血清浓度低于最低检测水平，但摄入BPA饲料的母鼠的血清浓度（5.48 ± 2.07 ng/ml）与在人类中观察到的浓度相当。总之，这些研究表明，发育暴露于环境相关浓度的BPA可以以剂量和性别依赖的方式破坏成年人的行为。
Bisphenol A (BPA) is a widely produced, endocrine disrupting compound that is pervasive in the environment. Data suggest that developmental exposure to BPA during sexual differentiation of the brain leads to later behavioral consequences in offspring. Outbred deer mice (Peromyscus maniculatus bairdii) are an excellent animal model for such studies as they exhibit well-defined sex- and steroid-dependent behaviors. Here, dams during gestation and lactation were fed a phytoestrogen-free control diet, the same diet supplemented with either ethinyl estradiol (0.1 parts per billion), or one of three doses of BPA (50 mg, 5 mg, 50 μg/kg feed weight). After weaning, pups were maintained on control diet until they reached sexually maturity and then assessed for both spatial learning capabilities and anxiety-like and exploratory behaviors. Relative to controls, males exposed to the two upper but not the lowest dose of BPA demonstrated similar impairments in spatial learning, increased anxiety and reduced exploratory behaviors as ethinyl estradiol-exposed males, while females exposed to ethinyl estradiol, but not to BPA, exhibited masculinized spatial abilities. We also determined whether dams maintained chronically on the upper dose of BPA contained environmentally relevant concentrations of BPA in their blood. While serum concentrations of unconjugated BPA in controls were below the minimum level of detection, those from dams on the BPA diet were comparable (5.48 ± 2.07ng/ml) to concentrations observed that have been observed in humans. Together, these studies demonstrate that developmental exposure to environmentally relevant concentrations of BPA can disrupt adult behaviors in a dose- and sex-dependent manner.
登录
查看更多内容
DOI：
10.1016/j.reprotox.2008.12.005
发表时间：
2009-04
期刊：
Reproductive toxicology (Elmsford, N.Y.)
影响因子：
--
作者：
Delclos KB;Weis CC;Bucci TJ;Olson G;Mellick P;Sadovova N;Latendresse JR;Thorn B;Newbold RR
通讯作者：
Newbold RR
影响因子：
3.5
作者：
Doerge, Daniel R.;Twaddle, Nathan C.;Fisher, Jeffrey W.
通讯作者：
Fisher, Jeffrey W.
影响因子：
2.9
作者：
GALEA, LAM;KAVALIERS, M;HARGREAVES, EL
通讯作者：
HARGREAVES, EL
影响因子：
2.3
作者：
CLARKE, JA
通讯作者：
CLARKE, JA
影响因子：
3.6
作者：
Fountain, Emily D.;Mao, Jiude;Rosenfeld, Cheryl S.
通讯作者：
Rosenfeld, Cheryl S.