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

产前双酚 A 暴露对绵羊复杂行为的改变

• 批准号: 8126451
• 负责人: THERESA M LEE
• 金额: $ 27.68万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-10 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8126451
• 关键词: Adolescence; Adolescent; Adult; Aggressive behavior; Androgens; Animals; Area; Behavior; Behavioral; Blood Circulation; Body Weight; Brain; Calculi; Child; Cognitive; Complex; Conceptions; Data; Development; Disease; Dose; Drug Addiction; Endocrine Disruptors; Endocrine system; Environment; Estrogens; Exposure to; Female; Fetus; Fright; Future; Goals; Gonadal Steroid Hormones; Gossypium; Grant; Health; Human; Infertility; Learning; Life; Longevity; Modeling; Mothers; Motivation; Organ; Partner in relationship; Physiological; Physiology; Placenta; Plastics; Play; Predisposition; Reproduction; Research Design; Research Personnel; Resources; Rodent; Role; Savings; Sex Behavior; Sheep; Social Behavior; Societies; Steroid Receptors; Steroids; Stimulus; Stress; System; Testosterone; United States National Institutes of Health; Work; bisphenol A; critical period; experience; exposed human population; in utero; male; neurochemistry; offspring; pollutant; polycarbonate; prenatal; prenatal exposure; public health relevance; receptor; reproductive; reproductive development; reproductive success; sex; social; steroid hormone; steroid hormone receptor

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.

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。在产前发育过程中，暴露于此类污染物可能会对发育中的胎儿产生不利影响，因为该系统在关键时期内具有高度塑性和反应性。最近，人们对这些污染物对子宫内胎儿的作用引起了很多关注。在环境中普遍存在的一种这样的化合物是双酚A（BPA）。它用于制作聚碳酸酯瓶，包括婴儿瓶和罐头的衬里，因此暴露是广泛的。对啮齿动物的研究已暗示产前BPA暴露在各种健康问题中。我们建议将绵羊用作模型来检查产前BPA对复杂行为的影响。与产前睾丸激素接触的类似工作表明，绵羊是此类研究的绝佳模型。使用绵羊作为产前BPA暴露的模型的研究表明，对BPA的暴露会导致生殖破坏。但是，尚未做任何工作来研究长期寿命的社会物种（例如我们自己）中复杂行为的寿命发展。这项研究的目的是研究产前BPA暴露和青少年BPA暴露对整个发育过程中绵羊模型中复杂行为的影响。这些行为将与包括类固醇激素水平，压力反应性和体重在内的生理终点相关。此外，我们将检查与动机和交配行为完善相关的大脑区域中类固醇受体的数量和分布。我们假设在类似于人类胎儿暴露的水平上，产前暴露于BPA，将破坏各种复杂行为，包括动物的寿命，包括游戏，侵略性，动机和性行为。第二阶段的脆弱性是青春期，因此我们还将检查青春期BPA暴露的影响。与对照组相比，具体目的1和2将检查男性和女性的整个寿命中的复杂行为，这些行为均暴露于产前，青少年或产前和青少年BPA。具体目标3将检查这些脆弱时期内BPA暴露对类固醇受体数量和分布与动机和交配行为完善相关的大脑区域的影响。这项研究的结果对于表征产前暴露于内分泌破坏者BPA的行为和发育效果很重要。这是社会上的一个重要问题，因为许多母亲和幼儿暴露于BPA的产品。 公共卫生相关性：一种干扰化学物质的双酚A（BPA）在工业化世界中广泛使用。特别关心的是在生殖发育的关键时期的影响，包括子宫和青少年暴露于BPA，这可能会产生有害的生理和行为影响。该项目将研究绵羊模型中产前BPA暴露的行为和神经化学作用。