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

终生接触低剂量双酚 A 对非洲爪蟾发声通路发育和使用的影响

• 批准号: 10428869
• 负责人: Ian Christopher Hall
• 金额: $ 38.19万
• 依托单位: BENEDICTINE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-05 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10428869
• 关键词: Acute; Adolescence; Adolescent; Adult; American; Animal Model; Automobile Driving; Behavior; Behavioral; Brain; Centers for Disease Control and Prevention (U.S.); Chemical Exposure; Child; Chronic; Complement; Data; Development; Dose; Economics; Endocrine; Endocrine Disruptors; Endocrine disruption; Environment; Exposure to; Female; Fetus; Future; Goals; Growth; Health; Home; Human; Human Development; In Vitro; Investigation; Knowledge; Language; Language Development; Language Disorders; Larynx; Lead; Life; Literature; Long-Term Effects; Longevity; Modeling; Monitor; Morphology; Motor; Output; Paper; Pathway interactions; Pattern; Physiological; Population; Pregnancy; Preparation; Rana; Reading; Reporting; Research; Social Environment; South African; Speech Pathology; Speech Therapy; Structure; System; Tadpoles; Time; United States National Institutes of Health; Urine; Variant; Vocabulary; Work; Xenopus; Xenopus laevis; bisphenol A; boys; experimental study; fictional works; hazard; human male; in utero; in vivo; insight; male; neural circuit; neurophysiology; novel; prenatal exposure; relating to nervous system; sex; skill acquisition; skills; social; sound; success; tool; undergraduate student; vocalization; zygote

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.

项目摘要 内分泌干​​扰化学物质（EDC）是已知的危害，在 环境和人类家中。双苯酚A（BPA）是共同发现的已知EDC 从塑料到纸质收据的项目。最近的证据表明，BPA存在于 美国人的水平足够高，可以对男性的语言获取造成不利影响， 人类的孩子。尽管这样的水平被认为是安全的，成人暴露，但影响 在开发过程中长期，低剂量暴露于EDC是一种研究的现象 可能对人类健康产生严重影响。 这项研究的目的是：1）跟踪低剂量BPA暴露的影响 成年后的发展，2）确定引起的人声缺陷的机制 通过内分泌干扰。拟议的研究包括少年发育的体内分析 和行为过渡到成人声音行为模式。体内工作是 补充喉的体外分析和大脑中的神经结构 动力发声。 这些研究利用南非爪蛙Xenopus laevis作为模型 生物。驱动X. laevis发声模式的机制经过了充分研究，它们的 人声行为多种多样，但并不复杂。 X. Laevis至少生产七种不同类型的 发声;有些是男性特异性的，有些是特定于女性的，并且全部用于特定的 社会环境。呼叫是先天的事实，这种变化是人声模式的平衡 并且不需要学习。 Xenopus的声音行为很容易量化。呼叫具有不同的功能 他们很容易被视为不同的单位。每个呼叫也都由具有独特的声音组成 时间和光谱特征也可以进行量化以进行比较。时间和 发声的光谱成分是由大脑中的声带发生器产生的 喉部内的共振结构（分别）和两个结构都在 允许机械研究的体外制剂。因此，X. laevis人声系统很好 诸如BPA之类的EDC进行语言中断的研究，因为畸变很容易 可以直接研究确定的和近端原因。这项调查将提供洞察力 BPA如何影响语言发展，使我们能够确定语音的潜在目标 治疗以及强调长期，低剂量暴露于EDC的潜在危害。