Department of Operative Dentistry, School of Dentistry, University of Athens, Greece.
Neuroscience. 2010 May 19;167(3):741-9. doi: 10.1016/j.neuroscience.2010.02.051. Epub 2010 Feb 26.
The estrogen-mimicking endocrine disrupter bisphenol A (BPA) which is used in the manufacture of plastic and epoxy resins, is one of the world's most heavily produced synthetic chemicals. BPA is detected in animal tissues, and its bio-accumulation has shown to be higher in the fetus than the mother. Exposure to doses below the daily safe limit has been reported to affect the sexual differentiation of the brain and modify the behavior of the exposed rodent offspring. The aim of the present study was to investigate in the rat the possible organizational effects of low BPA exposure on glucocorticoid-regulated responses. Female breeders were exposed to 40 microg/kg b.w. BPA daily throughout pregnancy and lactation. Plasma corticosterone levels and the two types of hippocampal corticosteroid receptors (GR and MR) were determined in mid-adolescent offspring under basal conditions and following a Y-maze task. BPA treated females had higher corticosterone levels than control females and BPA males and lower GR levels than BPA males, under basal conditions. Following the mildly stressful experience of Y-maze, corticosterone levels were increased in BPA-treated animals of both sexes, compared to the controls. GR levels were also increased in BPA-treated females compared to males. No effect of BPA was observed on MR levels, whereas the Y-maze experience significantly decreased receptors' levels in both female groups. The animals' performance in the task was also evaluated. BPA exposure significantly impaired the spatial recognition memory in both sexes, and modified the behavioural coping in a sex-dependent manner. Female BPA-treated offspring exhibited increased "anxiety-like" behaviour and dramatic loss of exploration attitude during the task, in comparison to males. This study provides for the first time evidence that corticosterone and its actions in the brain are sensitive to the programming effects of BPA at a dose below the currently acceptable daily intake.
双酚 A（BPA）是一种具有雌激素模拟作用的内分泌干扰物，被广泛用于塑料和环氧树脂的制造，是世界上产量最大的合成化学品之一。BPA 已在动物组织中被检测到，其生物蓄积性在胎儿中比在母体中更高。据报道，即使接触低于每日安全限量的剂量，也会影响大脑的性分化，并改变暴露于其中的啮齿动物后代的行为。本研究旨在调查低剂量 BPA 暴露对糖皮质激素调节反应的可能组织效应。雌性繁殖者在整个怀孕期间和哺乳期每天接受 40μg/kg b.w. BPA 暴露。在青春期中期，根据基础条件和 Y 型迷宫任务，确定了其后代的血浆皮质酮水平和两种类型的海马皮质类固醇受体（GR 和 MR）。BPA 处理的雌性动物的皮质酮水平高于对照组雌性动物和 BPA 雄性动物，而基础条件下的 GR 水平低于 BPA 雄性动物。在 Y 型迷宫轻度应激体验后，与对照组相比，BPA 处理的动物的皮质酮水平升高。BPA 处理的雌性动物的 GR 水平也比雄性动物升高。BPA 对 MR 水平没有影响，而 Y 型迷宫体验显著降低了两组雌性动物的受体水平。还评估了动物在任务中的表现。BPA 暴露显著损害了两性动物的空间识别记忆，并以性别依赖的方式改变了行为应对方式。与雄性动物相比，BPA 处理的雌性后代在任务中表现出增加的“焦虑样”行为和探索态度的显著丧失。本研究首次提供证据表明，皮质酮及其在大脑中的作用对 BPA 的编程效应敏感，BPA 的剂量低于目前可接受的每日摄入量。
