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.

项目概要 内分泌干​​扰化学物质 (EDC) 是已知的危害，在以下领域仍然普遍存在： 环境和人类家庭。双酚 A (BPA) 是一种常见的 EDC 从塑料收据到纸质收据。最近的证据表明 BPA 存在于 美国人的水平足以对男性语言习得造成不利影响， 人类的孩子。尽管这样的水平对于成人急性接触来说被认为是安全的，但其影响 在发育过程中长期、低剂量暴露于 EDC 的现象是一个尚未得到充分研究的现象 对人类健康有潜在的严重影响。 本研究的目的是： 1) 追踪低剂量 BPA 暴露对整个人群的影响 发育到成年，以及 2) 确定引起声音缺陷的潜在机制 通过内分泌干扰。拟议的研究包括青少年发育的体内分析 以及他们转变为成人声音行为模式时的行为。体内功是 辅以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蛙（Xenopus laevis）作为模型 生物。驱动 X. laevis 发声模式的机制已得到充分研究，并且它们的 声音行为多种多样，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，并且全部用于特定用途 社会背景。声音模式的变化是通过呼叫是天生的这一事实来平衡的 并且不需要学习。 非洲爪蟾的发声行为很容易量化。呼叫具有独特的特征，使得 它们很容易被算作不同的单位。每个呼叫也由具有不同特征的声音组成 时间和光谱特征也可以量化以进行比较。时间和 发声的频谱成分是由大脑中的声音模式发生器生成的 和喉内的共振结构（分别），并且这两种结构都具有鲁棒性 允许进行机械研究的体外制剂。因此，X. laevis 的发声系统很好 适合研究 BPA 等 EDC 造成的语言干扰，因为畸变很容易发生 可以直接调查已识别的近因。这项调查将提供见解 BPA 如何影响语言发展，使我们能够识别潜在的言语目标 治疗并强调长期、低剂量接触 EDC 的潜在危害。