| Environmental endocrine disrupting chemicals, a kind of substances existing in the environment, can simulate the natural hormones and disrupt the normal function of the endocrine system, including hormone synthesis, secretion, transporting, binding, biological effects and removal. It impacts the growth and long-term function of the hormone-sensitive tissue, particularly in the formation and development stage of the tissue(such as gestation and neonatal period). It causes a great deal of threat to human health and wildlife. Bisphenol A (BPA) is one of the typical environmental endocrine disruptors. It is widely used to manufacture polycarbonate plastic, epoxy resin, polystyrene resin, fungicide antioxidant, dye and packaging material for food. It has been continue to develop new uses. BPA leaches from the lining of tin cans into foods, from dental sealants into saliva, and from polycarbonate bottles into their contents. With a large number of plastics widely using, BPA caused serious environmental pollution. BPA has both estrogenic and anti-estrogenic action. Perinatal exposure to BPA profoundly disrupts structure and development of the brain cortex and the morphological development of hippocampal neuron. It means that the developing brain is a sensitive target organ to BPA. Endogenous estrogen can effect spontaneous activity, exploration behavior, anxiety behavior, learning and memory behavior of animals. NMDA glutamate receptor is widely spread in the brain. It's necessary to all the excitatory post-synaptic components. It participates in many complex physiological processes, such as the induction of the long-term potentiation, learning and memory behavior, regulation of neuronal survival and migration, controlling the growth of the structure of neural circuit , dendrites , axon and the plasticity of the synatic . Many studies have focused on the toxicity to the reproductive system and development, less on the central nervous system and non reproductive system. Therefore, it is envisaged that BPA may interfere with the changes of the offspring's non-reproductive behaviors and learning memory. Then, is the NMDA receptor protein which is in relation to the long-term potentiation and learning and memory behavior changed? Our study discusses about the problem.In the present study, pregnant dams were orally exposed to BPA dissolved in peanut oil (0.05, 0.5, 5 or 50 mg/kg/d) or only peanut oil as a vehicle control from gestational day (GD) 7 to postnatal day (PND) 21. Open field behavior, elevated plus-maze, Morris water maze, step down test and Western Blot were respectively used to investigate impacts of exposure to BPA on the offspring mice, gender differences in non-reproductive behavior in particular, as well as brain changes in the expression of NMDA receptor.The behavior of offspring at PND 21 and PND 56 of age were first tested using open field, elevated plus-maze, Morris water maze, and step down test. They 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 (P<0.05 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/d (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/d BPA increased the frequency of error and reduced the latency of stepping down from the platform in PND 21 male; and 50 mg/kg/d BPA increased the frequency of error and reduced the latency of stepping down from the platform in PND 56 male and female offspring.In order to investigate the relevance between non-reproductive behaviors and the expression of NMDA receptor, we did research on the expression of NMDA receptor in brain cortex and hippocampus in mice of different sexes. The results showed that exposure to BPA reduced the protein expression of NMDA receptor subunits in brain cortex and hippocampus of different sexes mice (P<0.05 or P<0.01) , 0.5～50mg/kg/d BPA groups showed significances.The results mentioned above indicate that perinatal exposure to BPA can affect non-reproductive behavior of the offspring mice and adult during developmental stages. And there are gender differences in the impact of these behaviors. Meanwhile, BPA impacts on the protein expression of MNDA receptor changes in cerebral cortex and hippocampus of offspring mice, different doses make different degrees.Summarily, A variety of behaviors were affected by perinatal exposure to BPA. There are gender differences in different behaviors. At the same time, BPA impacts the expression of the NMDA glutamate receptor. These results suggested that the behavior changes of offspring mice by BPA exposure is related to the expression changes of NMDA receptor. |
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