Environmental Endocrine Disruption in Avian WildlifeEPA Grant Number: R826298
Title: Environmental Endocrine Disruption in Avian Wildlife
Investigators: Lasley, Bill L. , Conley, Alan J. , Enan, Essam E. , Fry, D. Michael , Overstreet, James W.
Institution: University of California - Davis
EPA Project Officer: Reese, David H.
Project Period: February 1, 1998 through January 31, 2001
Project Amount: $437,544
RFA: Endocrine Disruptors (1997) RFA Text | Recipients Lists
Research Category: Economics and Decision Sciences , Endocrine Disruptors , Health , Safer Chemicals
Description:The overall objective of this project is to characterize the mechanisms by which halogenated aromatic hydrocarbons (HAH) cause disruption of growth factor and steroid hormone signal transduction in the cells of avian wildlife species. Our general hypothesis is that the primary mechanism of toxic action of HAHs involves their activation of cytosolic phosphorylation transduction pathways by which steroid hormones and growth factors communicate their signal to the cell nucleus. Male and female mammals have different sensitivities to the toxic effects of HAHs which have been shown to be related to gender-specific differences in the mechanisms of toxicity at the cellular level. We hypothesize that similar gender differences in susceptibility to toxicity can be demonstrated in avian species. Since both growth factors and sex steroids are required for normal sexual differentiation and lower vertebrate species have more developmental plasticity than mammals, we further hypothesize that avian species will be more vulnerable to disruption of endocrine signaling during critical stages of sexual development. Our specific objectives are to characterize the mechanisms of HAH toxicity at the cellular level in males and females of two avian species, to determine the relationship of sex steroid hormone signaling to the toxic actions of HAHs and provide evidence that disruption of growth factor and hormone signals can interfere with sexual differentiation in avian species.
Approach:Experiments will be performed using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a model compound. In vivo toxicity studies will be carried out with chickens and in vitro studies will be performed with tissues from chickens and gulls. We will determine if TCDD causes a wasting syndrome in birds, we will characterize the biochemical mechanisms of this toxicity and we will determine which gender is more susceptible to these adverse effects. We will characterize the mitotic signal transduction pathways that mediate TCDD-induced toxicity in birds and determine if these pathways are shared with those of sex steroid hormones and growth factors. We will determine how the toxicity signal induced by TCDD can interfere with the normal regulation of nuclear transduction pathways. Embryos of chickens and gulls will be treated with TCDD in combination with sex steroids to demonstrate an effect of HAHs on sexual differentiation through interference with endocrine signal transduction.
Expected Results:The results of these experiments will demonstrate a mechanism of HAH toxicity to avian wildlife and determine the relative sensitivities of males and females to these toxic effects. Specifically, these data will reveal the degree of overlap in the signal transduction pathways of growth factors, steroid hormones and HAHs, and provide strong evidence that this overlap is central to the toxic action of this class of endocrine disruptors. The principal benefit of this project is that it addresses directly endocrine disruptor-related effects in wildlife populations. Additionally, it focuses on mechanisms of the toxicity of endocrine disruptors at the cellular and molecular levels. The project will identify sensitive subpopulations as well as effects on sexual differentiation and reproductive development. All of these features of the project are highly responsive to the research needs of EPA.
Publications and Presentations:Publications have been submitted on this project: View all 7 publications for this project
Journal Articles:Journal Articles have been submitted on this project: View all 4 journal articles for this project
Supplemental Keywords:Avian, Toxicology, Environmental Hazard, Cellular, Endocrine., RFA, Health, Scientific Discipline, Toxics, Environmental Chemistry, Health Risk Assessment, pesticides, Endocrine Disruptors - Environmental Exposure & Risk, endocrine disruptors, Children's Health, Molecular Biology/Genetics, Biology, Endocrine Disruptors - Human Health, adverse outcomes, natural hormones, avian development, wildlife, TCDD, endocrine disrupting chemicals, exposure studies, steroid, 2, 3, 7, 8-Tetrachloro-dibenzo-p-dioxin (TCDD), HAH, animal models, developmental processes, halogenated aromatic hydrocarbons (HAH), reproductive processes, biological effects, hormone production, halogenated aromatic hydrocarbons, chickens
Progress and Final Reports:2000 Progress Report