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

Abstract

Bisphenol A (BPA) is one of the well-known environmental endocrine disrupters with mixed estrogen agonist/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 detection,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),increased grooming and rearing in male but decreased grooming and rearing in female offspring on PND 21(p0.05 or p 0.01). The results from elevated plus-maze displayed that,after perinatal exposure to BPA,the frequency 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 female offspring(p 0.05 or p 0.01); however,the influence of BPA on the behaviors of male and female offspring 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 offspring. 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 platform in PND 21 male; and 50 mg/kg/day BPA increased the frequency of error and reduced the latency of stepping 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 female offspring is more sensitive to perinatal exposure to BPA.