Gillette Ross, Reilly Michael P, Topper Viktoria Y, Thompson Lindsay M, Crews David, Gore Andrea C
Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, United States.
Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, United States.
Horm Behav. 2017 Jan;87:8-15. doi: 10.1016/j.yhbeh.2016.10.011. Epub 2016 Oct 26.
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 (0.5mg/kg or 1.0mg/kg, hereafter 1.0 and 0.5), estradiol benzoate (EB; 50μg/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.
接触多氯联苯（PCBs），一类内分泌干扰化学物质，可导致成年期生殖行为改变，尤其是在胎儿大脑性别分化的关键时期发生接触时。PCBs是否会改变其他性二态行为，如与焦虑相关的行为，目前了解甚少。为了解决这个问题，在妊娠第16天和18天，给怀孕的大鼠母鼠注射两次低剂量（0.5mg/kg或1.0mg/kg，以下简称1.0和0.5）的弱雌激素性多氯联苯混合物Aroclor 1221（A1221）、作为阳性雌激素对照的苯甲酸雌二醇（EB；50μg/kg）或溶剂（芝麻油中的3%二甲基亚砜）。我们还对F1代雄性和雌性后代的发育里程碑进行了全面评估。治疗对出生时的性别比例和睁眼年龄没有影响。通过雌性阴道开口和雄性包皮分离评估的青春期，在雌性中未受影响，但在接受A1221（1.0）治疗的雄性中提前。与对照组相比，接受A1221（两种剂量）治疗的雄性和雌性在成年早期体重更重。这种影响最早在青春期前的雄性中出现，在雌性中稍晚，在青春期出现。成年后使用明暗箱和高架十字迷宫试验测试焦虑样行为。在雌性中，焦虑行为不受治疗影响。接受A1221（1.0）治疗的雄性在明暗箱试验中焦虑指数降低、活动增加，但在高架十字迷宫试验中未出现这种情况。对于任何发育和行为终点，EB均未能复制A1221产生的表型。总体而言，这些结果表明，多氯联苯会增加两性的体重，但它们对焦虑样行为的影响具有雄性特异性。此外，A1221和EB结果之间的差异表明，多氯联苯可能通过与其雌激素活性不同的机制起作用。
