Alterations of complex behaviors in sheep by pre-natal bisphenol A exposure

描述(申请人提供)：内分泌干扰物(EDC)是扰乱内分泌系统正常功能的污染物。在出生前发育期间暴露于此类污染物会对发育中的胎儿产生有害影响，因为该系统在关键时期具有高度的可塑性和响应性。最近，人们非常关注这些污染物对子宫内胎儿的作用。在环境中普遍存在的一种这种化合物是双酚A(BPA)。它被用来制造聚碳酸酯瓶子，包括婴儿奶瓶和罐头衬里，因此接触广泛。对啮齿动物的研究表明，产前接触双酚A与各种健康问题有关。我们建议以绵羊为模型来研究产前双酚A对复杂行为的影响。类似的研究表明，绵羊是此类研究的极佳模型。在我们的设施中，使用绵羊作为产前暴露BPA的模型进行的研究表明，暴露于BPA会导致生殖中断。然而，目前还没有人研究像我们这样长寿的社会物种复杂行为的寿命发展。本研究的目的是研究产前双酚A暴露和青春期双酚A暴露对绵羊模型发育过程中复杂行为的影响。这些行为将与生理终点相关，包括类固醇激素水平、应激反应和体重。此外，我们还将研究类固醇受体在大脑中与交配行为的动机和完成相关的区域的数量和分布。我们假设，产前暴露于双酚A的水平与人类胎儿的暴露水平相似，将扰乱动物一生中的各种复杂行为，包括游戏、攻击性、动机和性行为。第二个脆弱时期是青春期，所以我们还将研究青春期接触双酚A的影响。具体目标1和2将检查男性和女性在整个生命周期中暴露于产前、青春期或产前和青春期双酚A的复杂行为，并与对照组进行比较。具体目标3将研究在这些脆弱时期接触BPA对与交配行为的动机和完成相关的大脑区域中类固醇受体数量和分布的影响。这项研究的结果对于表征产前暴露于内分泌干扰物BPA的行为和发育影响很重要。这是社会上的一个重要问题，因为母亲和幼儿接触到的许多产品都含有双酚A。

DESCRIPTION (provided by applicant): Endocrine disrupting chemicals (EDC) are pollutants that disturb normal functioning of the endocrine system. Exposure to such pollutants during pre-natal development can have detrimental effects on the developing fetus because the system is highly plastic and responsive during critical periods. There has been much concern recently about the action of these pollutants on fetuses in utero. One such compound that is prevalent in the environment is bisphenol A (BPA). It is used to make polycarbonate bottles, including baby bottles and linings of cans, so exposure is widespread. Studies in rodents have implicated prenatal BPA exposure in a variety of health problems. We propose to use sheep as a model to examine the effects of prenatal BPA on complex behaviors. Similar work with prenatal testosterone exposure has demonstrated that sheep are an excellent model for such studies. Studies at our facility using sheep as a model for prenatal BPA exposure indicate that exposure to BPA leads to reproductive disruptions. However, no work has yet been done to examine the lifespan development of complex behaviors in a long-lived social species, such as ourselves. The goal of this study is to investigate the effects of prenatal BPA exposure and adolescent BPA exposure on complex behaviors in the sheep model across development. These behaviors will be correlated with physiological endpoints including steroid hormone levels, stress reactivity and body weight. Additionally, we will be examining steroid receptor number and distribution in areas of the brain associated with motivation and consummation of mating behavior. We hypothesize that prenatal exposure to BPA, at levels similar to the exposure of human fetuses, will disrupt a variety of complex behaviors including play, aggressive, motivational and sex behaviors over the lifespan of the animal. A second period of vulnerability is adolescence, so we will also examine the effects of BPA exposure during adolescence. Specific Aims 1 and 2 will examine complex behaviors throughout the lifespan of both male and female exposed to either prenatal, adolescent or prenatal and adolescent BPA compared to controls. Specific Aim 3 will examine the effect of BPA exposure during these vulnerable periods on steroid receptor number and distribution in areas of the brain associated with motivation and consummation of mating behavior. Results from this study are important for characterizing the behavioral and developmental effects of prenatal exposure to the endocrine disruptor BPA. This is an important issue in society, since many products that mothers and young children are exposed to contain BPA.