The effects of life-long exposure to low doses of bisphenol A on the development and use of vocal pathways in X. laevis

项目摘要 内分泌干扰化学品（EDCs）是已知的危害， 环境和人类家园。双酚A（BPA）是一种常见的EDC， 从塑料到纸质收据。最近的证据表明，BPA存在于 美国人的水平高到足以对男性的语言习得造成不利影响， 人类的孩子虽然这样的水平被认为是安全的急性，成人接触， 在发育过程中长期、低剂量暴露于内分泌干扰物是一个未充分研究的现象 对人类健康有潜在的严重影响。 本研究的目的是：1）跟踪低剂量BPA暴露对 发展到成年，和2）确定潜在的发声缺陷的机制， 内分泌紊乱拟议的研究包括对青少年发育的体内分析 和行为转变成成年人的声音行为模式。体内工作是 辅以对喉部和大脑内神经结构的体外分析， 驱动发声。 这些研究利用南非爪蟾作为模型 有机体驱动X.耳鼻喉科的发声模式已得到充分研究， 发声行为多种多样，但并不复杂。X.莱维斯至少产生七种不同类型的 发声;有些是男性特有的，有些是女性特有的，所有这些都用于特定的 社会背景这种声音模式的变化与这种声音是天生的事实相平衡 不需要学习。 爪蟾的发声行为很容易量化。呼叫具有明显的特征， 它们很容易被视为不同的单位。每一种叫声也是由不同的声音组成的， 时间和光谱特征，也可以量化用于比较。时间和 发声的频谱成分是由大脑中的发声模式发生器产生的 和喉内的共鸣结构（分别），并且这两种结构都具有鲁棒性 允许进行机理研究的体外制剂。因此，X.左心耳发声系统良好 适合研究BPA等EDCs对语言的干扰，因为畸变很容易被 可以直接调查确定的和近端的原因。这项调查将提供深入了解 BPA如何影响语言发展，使我们能够识别潜在的语音目标 治疗以及强调长期，低剂量暴露于内分泌干扰物的潜在危害。

Project Summary Endocrine disrupting chemicals (EDCs) are known hazards which are still prevalent in the environment and in the human home. Bisphenol A (BPA) is a known EDC found in common items from plastic to paper receipts. Recent evidence suggests that BPA is present in Americans at levels high enough to cause detrimental effects on language acquisition in male, human children. Though such levels are considered safe for acute, adult exposure, the impact of long-term, low-dose exposure to EDCs during development is an understudied phenomenon with potentially serious impacts on human health. The aims of this study are to: 1) To track the impact of low-dose BPA exposure across development into adulthood, and 2) To identify the mechanisms underlying vocal deficits caused by endocrine disruption. The proposed studies include in vivo analyses of juvenile development and behavior as they transition into adult vocal behavior patterns. The in vivo work is complemented with in vitro analysis of the larynx and the neural structures within the brain that drive vocalization. These studies utilize the South African clawed frog, Xenopus laevis, as a model organism. The mechanisms driving X. laevis vocalization patterns are well-studied, and their vocal behaviors are varied but not complex. X. laevis produce at least seven different types of vocalization; some are male-specific, some are female-specific, and all are used in specific social contexts. The variation is vocal patterns is balanced by the fact that the calls are innate and do not need to be learned. Xenopus vocal behavior is easily quantified. Calls have distinct features which make them easily counted as distinct units. Each call is also composed of sounds that have distinct temporal and spectral features which can also be quantified for comparisons. The temporal and spectral components of vocalizations are generated by the vocal pattern generator in the brain and the resonance structures within the larynx (respectively,) and both structures have robust in vitro preparations that allow for mechanistic study. Thus, the X. laevis vocal system is well suited for studies of language disruption by EDCs like BPA, because aberrations are easily identified and proximal causes can be directly investigated. This investigation will provide insight how BPA impacts language development, allowing us to identify potential targets for speech therapy as well as highlighting the potential hazards of long-term, low-dose exposure to EDCs.