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 内分泌干扰物(EDCs)是已知的危险物质，在 对环境和人类家园的影响。双酚A(BPA)是一种已知的EDC，常见于 从塑料到纸质收据的物品。最近的证据表明，双酚A存在于 美国人的语言水平高到足以对男性的语言习得造成有害影响， 人类的孩子。尽管这样的水平被认为对成人急性接触是安全的，但其影响 在发育过程中长期、低剂量暴露于内分泌细胞是一个研究不足的现象 对人类健康有潜在严重影响。 这项研究的目的是：1)跟踪低剂量双酚A暴露的影响 发展到成年，以及2)确定导致发声障碍的机制 通过内分泌紊乱。建议的研究包括对青少年发育的活体分析。 以及当他们转变为成人发声行为模式时的行为。体内的工作是 辅以对喉部和大脑内神经结构的体外分析， 推动发声。 这些研究以南非爪蛙非洲爪蛙为模型 有机体。驱动莱维氏X.laevis发声模式的机制已经被很好地研究了，他们的 发声行为多种多样，但并不复杂。X.laevis产生至少七种不同类型的 发声；有些是男性专用的，有些是女性专用的，所有的都用于特定的 社会背景。这种不同的发声模式与叫声是与生俱来的事实相平衡 而且不需要学习。 非洲爪哇的发声行为很容易量化。呼叫具有不同的功能，使 它们很容易被算作不同的单位。每个呼叫也由不同的声音组成 时间和光谱特征，也可以量化以进行比较。世俗的和 发声的光谱成分是由大脑中的发声模式生成器产生的 而喉内的共振结构(分别)和两个结构在 能够进行机械性研究的体外制剂。因此，X.laevis的发声系统是很好的 适用于像BPA这样的EDC对语言干扰的研究，因为异常很容易 可以直接调查已确定的和最近的原因。这项调查将提供洞察 BPA如何影响语言发展，使我们能够确定潜在的演讲目标 治疗以及强调长期、低剂量暴露于内分泌细胞的潜在危险。

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.