Use of an Amphibian as an Alternative Model to Evaluate Effects of Contaminants o

使用两栖动物作为替代模型来评估污染物的影响

基本信息

批准号：
7365459
负责人：
Michelle Dawn Boone
金额：
$ 19.61万
依托单位：
MIAMI UNIVERSITY OXFORD
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-14 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7365459
关键词：
Academic Research Enhancement Awards Address Adolescent Affect Americas Amphibia Animals Atrazine Automobile Driving Behavior Behavior Disorders Behavioral Biochemical Biological Biological Metamorphosis Biopsy Brain Carbaryl Cell Proliferation Childhood Condition Development Developmental Process Disruption Ecosystem Elderly Embryonic Development End Point Endocrine system Environment Environmental Health Environmental Pollution Exposure to Future Gills Glucocorticoid Receptor Goals Growth Growth and Development function Health Herbicides Human Incidence Individual Insecticides Institution Journals Laboratories Lead Life Link Manuscripts Measures Metabolism Minority Modeling Molecular Organism Pathway interactions Peer Review Performance Population Precocious Puberty Predisposition Process Puberty Publications Rana Rana esculenta Rate Research Risk Role Science Sexual Development Skin Societies Staging Stress Students Support of Research Tadpoles Tail Techniques Testing Thyroid Diseases Thyroid Gland Thyroid Hormone Receptor Thyroid Hormones Time United States National Institutes of Health Universities Vertebrates Week Woman Work base cold temperature density design egg environmental stressor experience feeding field study food resource hatching infancy life history pathogen programs rapid growth reproductive development reproductive success research study response size success trait

项目摘要

DESCRIPTION (provided by applicant): The overarching goal of this research is to evaluate how the insecticide carbaryl alters thyroid hormone action, which in turn can influence critical developmental processes. We will use a non-mammalian, amphibian model because 1) amphibians undergo metamorphosis, which is under direct control of thyroid hormones; 2) amphibians are sensitive to environmental contaminants due to permeable eggs, gills, and skin; 3) previous work with amphibians has shown that exposure to the insecticide carbaryl can lead to precocious metamorphosis, which suggests thyroid hormone action is affected by exposure; and 4) the mechanisms whereby thyroid hormones enact their cellular effects are highly conserved in vertebrates, including humans. The proposed research will evaluate the central hypothesis that exposure to a sublethal concentration of an insecticide induces thyroid hormone action, which can negatively affect growth, development, behavior, and survival of individual anurans. To evaluate our hypothesis, we will examine the following specific objectives using molecular techniques, and laboratory and field studies with green frogs, Rana clamitans, reared from hatching through metamorphosis and into the terrestrial environment: (1) Evaluate the effects of exposure to the insecticide carbaryl on thyroid hormone action, and time to metamorphosis, size at metamorphosis, and survival to metamorphosis; (2) Examine how timing of exposure to carbaryl at different stages of development affects thyroid hormone action and incidence of precocious metamorphosis; (3) Determine the magnitude of the effect of carbaryl exposure on thyroid hormone action and metamorphosis under conditions of changing larval density, a stressful natural condition; and (4) Establish how larval exposure to carbaryl will influence later life stages by evaluating terrestrial performance of metamorphosed frogs. All animals may be particularly vulnerable to contaminants when they are undergoing cell proliferation or general remodeling of existing body plans (e.g., embryonic development, metamorphosis, infancy, childhood development, sexual development). Demonstrating that environmentally relevant concentrations of carbaryl can induce thyroid hormone action in both the laboratory and the field would offer powerful evidence to suggest that similar biochemical effects could occur in humans under natural conditions; this research will also indicate how natural environmental stressors may further increase susceptibility to effects of contaminants. The research outlined here will specifically address NIH goals linked to understanding processes related to human growth and development, and the biological effects of environmental contaminants using a non- mammalian model. Project Narrative: Demonstrating environmentally relevant concentrations of carbaryl can induce thyroid hormone action and that timing of development influences this response in an amphibian model would allow us to link contaminants to irreversible developmental changes that can influence brain development, rates of physical development, behavior, and future growth and survival. This research could suggest that humans may be most negatively affected by contaminant exposure during times of rapid growth and development, especially during embryonic development or onset of sexual maturity. Our proposed research uses an amphibian model and could help explain the role environmental contamination has in diverse phenomena such as thyroid diseases, behavior disorders, and early maturation in humans, all of which are or can be influenced by thyroid hormones.

描述（由申请人提供）：这项研究的总体目标是评估杀虫剂碳碳纤维如何改变甲状腺激素的作用，而甲状腺激素的作用又会影响关键的发育过程。我们将使用非哺乳动物的两栖动物模型，因为1）两栖动物经历了甲状腺激素的直接控制； 2）两栖动物由于可渗透的鸡蛋，g和皮肤而对环境污染物敏感； 3）以前与两栖动物的工作表明，暴露于杀虫剂碳碳纤维会导致早熟的变形，这表明甲状腺激素作用受到暴露的影响。 4）甲状腺激素发挥其细胞作用的机制在包括人类在内的脊椎动物中是高度保守的。拟议的研究将评估以下中心假设：暴露于杀虫剂的一定浓度会诱导甲状腺激素作用，甲状腺激素作用可能会对个别无动物的生长，发育，行为和存活产生负面影响。为了评估我们的假设，我们将使用分子技术研究以下特定目标，以及绿色青蛙，拉娜·克拉米氏菌的实验室和野外研究，从孵化到变质的孵化并进入陆地环境：（1）评估昆虫碳氧化物对甲状腺激素和甲状腺激素的影响，并在甲状腺激素动作和甲状腺囊泡上的影响，并在甲状腺激素上均可在甲状腺激素和甲状腺含量中，并在甲状腺中逐渐成分。（2）检查在不同发育阶段暴露于碳碳纤维的时间如何影响甲状腺激素的作用和早产的发生率；（3）确定在幼虫密度变化的条件下，碳脂暴露对甲状腺激素作用和变形的影响的大小，这是一种压力自然的条件；（4）确定幼虫暴露于碳碳纤维如何通过评估变态青蛙的陆地性能来影响以后的生活阶段。当所有动物经历细胞增殖或对现有身体计划的一般重塑时（例如胚胎发育，变态，婴儿期，儿童发育，性发育）时，所有动物都可能特别容易受到污染物的影响。证明与环境相关的碳碳纤维可以在实验室和田间诱导甲状腺激素作用，这将提供有力的证据，以表明在自然条件下人类中可能发生类似的生化作用。这项研究还将表明自然环境压力源如何进一步增加对污染物影响的敏感性。此处概述的研究将特别解决与了解与人类成长和发展相关的过程以及使用非哺乳动物模型的环境污染物的生物学效应有关的NIH目标。项目叙述：证明碳碳纤维的环境相关浓度可以诱导甲状腺激素作用，并且发展的时机在两栖动物模型中影响这种反应将使我们能够将污染物与不可逆的发展变化联系起来，从而影响大脑的发展，身体发育速度，行为，行为，行为，行为以及未来的成长和生存。这项研究可能表明，在快速生长和发育时期，尤其是在胚胎发育或性成熟期开始时，人类可能会受到污染物暴露的影响最大的。我们提出的研究使用两栖动物模型，可以帮助解释环境污染在各种现象中的作用，例如甲状腺疾病，行为障碍和人类早期成熟，所有这些现象都受到甲状腺激素的影响或可能影响甲状腺激素。