Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.
PLoS One. 2011;6(9):e25448. doi: 10.1371/journal.pone.0025448. Epub 2011 Sep 28.
Bisphenol A (BPA) is a man-made compound used to make polycarbonate plastics and epoxy resins; public health concerns have been fueled by findings that BPA exposure can reduce sex differences in brain and some behaviors. We asked if a low BPA dose, within the range measured in humans, ingested during pregnancy, would affect social behaviors in prepubertal mice. We noted sex differences in social interactions whereby females spent more time sitting side-by-side, while males engaged in more exploring and sitting alone. In addition BPA increased display of nose-to-nose contacts, play solicitations and approaches in both sexes. Interactions between sex and diet were found for self grooming, social interactions while sitting side-by-side and following the other mouse. In all these cases interactions were produced by differences between control and BPA females. We examined brains from embryos during late gestation to determine if gene expression differences might be correlated with some of the sexually dimorphic or BPA affected behaviors we observed. Because BPA treatments ended at birth we took the brains during embryogenesis to increase the probability of discovering BPA mediated effects. We also selected this embryonic age (E18.5) because it coincides with the onset of sexual differentiation of the brain. Interestingly, mRNA for the glutamate transporter, Slc1a1, was enhanced by exposure to BPA in female brains. Also we noted that BPA changed the expression of two of the three DNA methyltransferase genes, Dnmt1 and Dnmt3a. We propose that BPA affects DNA methylation of Sc1a1 during neural development. Sex differences in juvenile social interactions are affected by BPA and in particular this compound modifies behavior in females.
双酚 A（BPA）是一种人工合成的化合物，用于制造聚碳酸酯塑料和环氧树脂；公众健康的担忧源于发现 BPA 暴露会减少大脑和一些行为的性别差异。我们想知道在怀孕期间摄入的低剂量 BPA（在人类测量范围内）是否会影响青春期前小鼠的社交行为。我们注意到社交互动中的性别差异，即雌性花更多的时间并排坐着，而雄性则更多地独自探索和坐着。此外，BPA 增加了雌雄两性的鼻子对鼻子接触、玩耍请求和接近的次数。饮食与性别之间的相互作用表现在自我梳理、并排坐着的社交互动以及跟随另一只老鼠的行为上。在所有这些情况下，互动都是由对照组和 BPA 雌性之间的差异产生的。我们检查了妊娠晚期胚胎的大脑，以确定基因表达差异是否与我们观察到的一些性别二态或受 BPA 影响的行为有关。由于 BPA 治疗在出生时结束，我们在胚胎发生期间取脑，以增加发现 BPA 介导的影响的可能性。我们还选择了这个胚胎年龄（E18.5），因为它与大脑性分化的开始相吻合。有趣的是，暴露于 BPA 会增强雌性大脑中谷氨酸转运体 Slc1a1 的 mRNA。我们还注意到，BPA 改变了三种 DNA 甲基转移酶基因中的两种的表达，Dnmt1 和 Dnmt3a。我们提出，BPA 在神经发育过程中影响 Slc1a1 的 DNA 甲基化。青少年社交互动中的性别差异受 BPA 影响，特别是这种化合物会改变雌性的行为。
