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

描述（由申请人提供）：内分泌干扰化学物质（EDC）是干扰内分泌系统正常功能的污染物。在产前发育期间暴露于这些污染物会对发育中的胎儿产生有害影响，因为系统在关键时期具有高度可塑性和反应性。最近，这些污染物对子宫内胎儿的影响引起了很多关注。双酚A （BPA）是一种在环境中普遍存在的化合物。它被用来制造聚碳酸酯瓶，包括婴儿奶瓶和罐头衬里，所以暴露是普遍的。对啮齿动物的研究表明，产前BPA暴露与各种健康问题有关。我们建议用绵羊作为模型来研究产前BPA对复杂行为的影响。产前睾酮暴露的类似研究表明，绵羊是这类研究的绝佳模型。在我们的设施中，用绵羊作为产前BPA暴露模型的研究表明，BPA暴露会导致生殖中断。然而，目前还没有人研究像人类这样长寿的社会物种的复杂行为的寿命发展。本研究的目的是探讨产前BPA暴露和青春期BPA暴露对绵羊模型整个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、应激反应性和体重。此外，我们将检查类固醇受体的数量和分布在与动机和完成交配行为相关的大脑区域。我们假设，产前暴露于BPA的水平与人类胎儿的暴露水平相似，会在动物的一生中破坏各种复杂的行为，包括玩耍、攻击、动机和性行为。第二个易受伤害的时期是青春期，因此我们也将研究青春期BPA暴露的影响。具体目标1和2将研究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BPA的复杂行为与对照组相比。具体目标3将检查在这些脆弱时期BPA暴露对类固醇受体数量和分布的影响，这些区域与交配行为的动机和完成有关。本研究的结果对于描述产前暴露于内分泌干扰物双酚a对行为和发育的影响具有重要意义。这是一个重要的社会问题，因为母亲和幼儿接触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. PUBLIC HEALTH RELEVANCE: Bisphenol A (BPA), an endocrine disrupting chemical, is widely used in the industrialized world. Of particular concern is the effect during critical periods of reproductive development, including in utero and adolescent exposure to BPA, which can have detrimental physiological and behavioral effects. This project will examine the behavioral and neurochemical effects of prenatal BPA exposure in the sheep model.