权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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）：本研究的总体目标是评估杀虫剂西威因如何改变甲状腺激素的作用，进而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)两栖动物会经历蜕变，这是在甲状腺激素的直接控制下；2)两栖动物的卵、鳃和皮肤具有渗透性，对环境污染物敏感；3)先前对两栖动物的研究表明，接触杀虫剂西威因可导致早熟变态，这表明甲状腺激素的作用受到接触的影响；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高度保守。拟议的研究将评估中心假设，即暴露于亚致死浓度的杀虫剂会诱导甲状腺激素作用，这可能对个体的生长、发育、行为和生存产生负面影响。为了验证我们的假设，我们将使用分子技术，以及实验室和实地研究来检验以下特定目标，对绿蛙（Rana clamitans）进行研究，从孵化到变态，再到陆地环境：(1)评估暴露于杀虫剂西威因对甲状腺激素作用的影响，变态时间，变态大小和变态存活率；(2)研究不同发育阶段接触西威因的时间对甲状腺激素作用和早熟变态发生率的影响；(3)确定在自然应激条件下，在改变幼虫密度的条件下，西威因暴露对甲状腺激素作用和变态的影响程度；(4)通过评估蜕变蛙在陆地上的表现，确定暴露于西维因的幼虫对其后期生命阶段的影响。所有动物在经历细胞增殖或现有身体结构的一般重塑（如胚胎发育、变态、婴儿期、儿童期发育、性发育）时都可能特别容易受到污染物的影响。证明与环境有关的西威尼浓度可以在实验室和现场诱发甲状腺激素的作用，将提供强有力的证据，表明在自然条件下，类似的生化效应可能发生在人类身上；这项研究还将表明自然环境压力如何进一步增加对污染物影响的易感性。这里概述的研究将专门针对NIH的目标，以了解与人类生长和发育有关的过程，以及使用非哺乳动物模型的环境污染物的生物效应。