ISSN 0439-755X
CN 11-1911/B

心理学报 ›› 2009, Vol. 41 ›› Issue (09): 832-841.

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  1. (1浙江师范大学化学与生命科学学院, 浙江金华 321004) (2浙江师范大学心理研究所, 浙江金华 321004)
  • 收稿日期:2009-01-08 修回日期:1900-01-01 出版日期:2009-09-30 发布日期:2009-09-30
  • 通讯作者: 徐晓虹

Perinatal Exposure to Bisphenol A Affects Sexual Differentiation of Behaviors in Offspring Mice

ZHANG Jing;XU Xiao-Hong;WANG Ya-Min;LUO Qing-Qing;YE Yin-Ping   

  1. (1 College of Chemistry and Life Science, Zhejiang Normal University, Jinhua 321004, China)
    (2 Psychology Research Center, Jinhua 321004, China)
  • Received:2009-01-08 Revised:1900-01-01 Online:2009-09-30 Published:2009-09-30
  • Contact: XU Xiao-Hong

摘要: 探讨围生期母体双酚A(bisphenol A, BPA)暴露对幼年期(生后21~30天, postnatal day 21~30, PND 21~30)和青年期(生后56~63天, PND 56~63)不同性别子代小鼠行为的影响。母鼠从妊娠第7天至断乳前(产后21天)进行BPA(0.05、0.5、5、50 mg/kg/day)灌胃染毒, 同时设对照组。每个剂量组分别在PND 21和PND 56开始测试雌雄子代小鼠各项行为。以旷场行为检测小鼠的自发活动及探究行为, 以高架十字迷宫检测小鼠的焦虑行为, 以水迷宫检测小鼠的空间学习记忆能力, 以跳台检测小鼠的被动回避记忆行为。结果表明, BPA使PND 21雌雄子鼠和PND 56雄性子鼠自发活动减少(p<0.05或p<0.01), 理毛和站立行为发生性别分化(p<0.05或p<0.01); PND 21子鼠的3分钟跑动格数有明显的剂量效应关系, 其中5~50 mg/kg/day组特别显著。BPA显著增加PND 21雌雄子鼠和PND56雌性子鼠在高架十字迷宫中进入开放臂次数和停留时间(p<0.05或p<0.01)并减少封闭臂的进入时间, 但没有明显的剂量效应关系; BPA减少PND 56雄性子鼠开放臂的进入并增加其封闭臂的进入, 干扰了幼年期和青年期小鼠焦虑行为的性别分化。BPA剂量依赖性地延长PND 21和PND 56雄性子鼠在水迷宫搜索平台的平均距离, 其中5~50 mg/kg/day剂量组具有差异显著性(p<0.05或p<0.01), 但对雌性子鼠空间学习记忆行为没有影响。此外, 5~50 mg/kg/day BPA增加PND 21雄性子鼠在跳台实验中的错误次数并缩短其跳下平台潜伏期, PND 56雌雄子鼠的被动回避记忆仅被50 mg/kg/day BPA减弱。以上结果提示, 围生期BPA暴露可影响子代小鼠幼年期和青年期的多种行为及行为的性别差异, 不同行为对BPA的敏感程度不同, 其中以自发活动和探究行为最敏感。

关键词: 双酚A, 行为, 性别差异

Abstract: Bisphenol A (BPA) is one of the well-known environmental endocrine disrupters with mixed estrogen ago-nist/antagonist properties. Although many studies have focused on the toxicity to the reproductive system and development, less on the central nervous system. Published results have demonstrated that perinatal exposure to low doses of BPA (below the human tolerable daily intake level, <0.05 mg/kg/day) does not affect reproductive system, but affects sexual behavior, social behavior, and other neurobehaviors. The purpose of this study was to investigate whether perinatal maternal exposure to BPA affects sexual differentiation of behaviors in offspring mice.
After acclimatization for one week, adult female ICR mice were placed with males (two females:one male) and vaginal smears were examined daily. A sperm-positive smear determined gestational day (GD) 0. After de-tection, pregnant dams were orally exposed to BPA dissolved in peanut oil (50, 5, 0.5 or 0.05 mg/kg/day) or only peanut oil as a vehicle control from gestational day(GD) 7 through postnatal day (PND) 21. At PND 21 and PND 56 of age, open field, elevated plus-maze, Morris water maze, and step down were respectively used to test spontaneous activity and exploratory behavior, anxiety, spatial learning and memory, and passive avoidance memory in offspring mice.
The results showed that perinatal exposure to BPA significantly inhibited the growth of body weight of male and female offspring (p <0.001). The results from open field showed that BPA decreased the spontaneous activity of male offspring on PND21 and PND 56 and female offspring on PND 21(p <0.05 or p <0.01), in-creased grooming and rearing in male but decreased grooming and rearing in female offspring on PND 21(p <0.05 or p <0.01). The results from elevated plus-maze displayed that, after perinatal exposure to BPA, the fre-quency of open arms entrance and stayed time in the open arms were dose-independently increased, but stayed time in the closed arm was dose-independently decreased in the PND 21 male and female and the PND 56 fe-male offspring(p <0.05 or p <0.01); however, the influence of BPA on the behaviors of male and female off-spring on PND 56 was different, with increased entrance of the open arms and decreased entrance of the closed arm in female, and decreased entrance of the open arm and increased entrance of the closed arm in male off-spring. The results of Morris water maze test showed that BPA dose-dependently increased the distances to find the platform in the water maze of PND 21 and PND56 male, especially under the dose of 5~50 mg/kg/day(p <0.05 or p <0.01), but no significant influence was found in the female mice. In addition, in the step down test, 5~50 mg/kg/day BPA increased the frequency of error and reduced the latency of stepping down from the plat-form in PND 21 male; and 50 mg/kg/day BPA increased the frequency of error and reduced the latency of step-ping down from the platform in PND 56 male and female offspring.
These results suggest that perinatal maternal exposure to BPA affects sexual differentiation of behaviors during the puberty and adulthood of offspring mice. The spontaneous activity and exploratory behavior, spatial learning and memory, and passive avoidance memory in male offspring are more sensitive, while anxiety in fe-male offspring is more sensitive to perinatal exposure to BPA.

Key words: bisphenol A, behavior, sex differentiation