Anxiety-like behaviors in adulthood are altered in male but not female rats exposed to low dosages of polychlorinated biphenyls in utero.

Anxiety-like behaviors in adulthood are altered in male but not female rats exposed to low dosages of polychlorinated biphenyls in utero.
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DOI:
10.1016/j.yhbeh.2016.10.011
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发表时间:
2017-01
影响因子:
3.5
通讯作者:
Gore AC
Gore AC
中科院分区:
医学3区
文献类型:
--
作者:
Gillette R;Reilly MP;Topper VY;Thompson LM;Crews D;Gore AC

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暴露于多氯联苯(PCBs),一类内分泌干扰化学品,可导致成年后生殖行为的改变,特别是当暴露发生在胎儿大脑性别分化的关键时期时。多氯联苯是否会改变其他性二态行为,如焦虑症,目前还知之甚少。为了解决这一问题,在妊娠第16天和第18天,对妊娠大鼠母鼠注射两次弱雌激素PCB混合物Aroclor 1221(A1221),剂量为两种低剂量(0.5 mg/kg或1.0 mg/kg,以下为1.0和0.5)之一,苯甲酸雌二醇(EB; 50 μg/kg)作为阳性雌激素对照,或溶剂(3% DMSO的芝麻油溶液)。我们还对F1雄性和雌性后代的发育里程碑进行了全面评估。治疗对出生性别比和睁眼年龄无影响。通过雌性动物阴道张开和雄性动物包皮分离评估的青春期在雌性动物中不受影响,但在A1221(1.0)处理的雄性动物中提前。与对照组相比,接受A1221(两种剂量)给药的雄性和雌性动物在成年早期体重更重。这种效应的最早表现在青春期之前的男性和女性稍晚,在青春期。在成年期使用光:暗箱和高架十字迷宫测试来测试类迷宫行为。在雌性动物中,焦虑行为不受治疗影响。接受A1221(1.0)给药的雄性动物显示焦虑指数降低,且在光暗箱中的活动增加,但在高架十字迷宫中未显示。EB未能复制A1221产生的任何发育和行为终点的表型。总的来说,这些结果表明,多氯联苯增加体重在两种性别,但他们的焦虑样行为的影响是特定的男性。此外,A1221和EB的结果之间的差异表明,多氯联苯可能通过不同于其雌激素活性的机制发挥作用。
Exposure to polychlorinated biphenyls (PCBs), a class of endocrine-disrupting chemicals, can result in altered reproductive behavior in adulthood, especially when exposure occurs during critical periods of brain sexual differentiation in the fetus. Whether PCBs alter other sexually dimorphic behaviors such as those involved in anxiety is poorly understood. To address this, pregnant rat dams were injected twice, on gestational days 16 and 18, with the weakly estrogenic PCB mixture Aroclor 1221 (A1221) at one of two low dosages (0.5 mg/kg or 1.0 mg/kg, hereafter 1.0 and 0.5), estradiol benzoate (EB; 50 μg/kg) as a positive estrogenic control, or the vehicle (3% DMSO in sesame oil). We also conducted a comprehensive assessment of developmental milestones of the F1 male and female offspring. There were no effects of treatment on sex ratio at birth and age at eye opening. Puberty, assessed by vaginal opening in females and preputial separation in males, was not affected in females but was advanced in males treated with A1221 (1.0). Males and females treated with A1221 (both dosages) were heavier in early adulthood relative to controls. The earliest manifestation of this effect developed in males prior to puberty and in females slightly later, during puberty. Anxiety-like behaviors were tested using the light:dark box and elevated plus maze tests in adulthood. In females, anxiety behaviors were unaffected by treatment. Males treated with A1221 (1.0) showed reduced indices of anxiety and increased activity in the light:dark box but not the elevated plus maze. EB failed to replicate the phenotype produced by A1221 for any of the developmental and behavioral endpoints. Collectively, these results indicate that PCBs increase body weight in both sexes, but their effects on anxiety-like behaviors are specific to males. Furthermore, differences between the results of A1221 and EB suggest that the PCBs are likely acting through mechanisms distinct from their estrogenic activity.
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发表时间: 2006-06-01
期刊: ENDOCRINOLOGY
影响因子: 4.8
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发表时间: 1991-02-01
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发表时间: 1999-11-01
影响因子: 10.4
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发表时间: 1995-01-01
影响因子: 5.8
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