2000 Progress Report: Neuroendocrine Mechanisms of Environmental Toxicants: PCBs and PesticidesEPA Grant Number: R827039C005
Subproject: this is subproject number 005 , established and managed by the Center Director under grant R827039
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Mount Sinai Center for Children's Environmental Health and Disease Prevention Research
Center Director: Wolff, Mary S.
Title: Neuroendocrine Mechanisms of Environmental Toxicants: PCBs and Pesticides
Investigators: Gore, Andrea , Wolff, Mary S.
Institution: Mount Sinai School of Medicine
EPA Project Officer: Callan, Richard
Project Period: August 1, 1998 through July 31, 2003 (Extended to July 31, 2004)
Project Period Covered by this Report: August 1, 1999 through July 31, 2000
Project Amount: Refer to main center abstract for funding details.
RFA: Centers for Children's Environmental Health and Disease Prevention Research (1998) RFA Text | Recipients Lists
Research Category: Children's Health , Health Effects , Health
Initial studies have focused on the GT1-7 cell line. The five proposed environmental toxicants, Aroclor-1221, Aroclor-1254, methoxychlor, chlorpyrifos, and lead were administered to GT1-7 cells. Gonadotropin releasing hormone (GnRH) neuronal morphology and GnRH gene expression were measured in response to these substances. The greatest effects were caused by Aroclor-1221, Aroclor-1254, and methoxychlor, which had significant effects on GT1-7 cell morphology and GnRH mRNA levels. Aroclor-1221 caused a stimulation of GnRH gene expression and neurite outgrowth, while Aroclor-1254 and methoxychlor inhibited these parameters. We are continuing these studies in time-course and dose-response experiments.
We have also initiated a program evaluating effects of the five toxicants on pubertal development and GnRH gene expression in developing female rat pups. Each of the toxicants or a vehicle was injected daily beginning the day after birth and for the next 2 weeks. Rats were monitored for pubertal events such as the timing of vaginal opening, which indicates a hormonal surge prior to puberty, and for first diestrus, which indicates that ovulation has occurred. We killed rats at various times after first diestrus and measured GnRH mRNA utilizing the RNase protection assay.
The results indicated that none of the toxicants significantly altered the timing of pubertal events or affected GnRH mRNA levels. Therefore, we have decided to focus our future studies on rats that are exposed in utero to the environmental toxicants. Pregnant Sprague-Dawley rats have been injected on day 15 of embryonic development with one of the toxicants. They are allowed to give birth, and pups are monitored for pubertal development and GnRH gene expression is measured. We are in the midst of performing these studies. Results are quite promising since a number of the toxicants have caused significant changes in the timing of pubertal events (vaginal opening and first diestrus) and in body weight. At the conclusion of these experiments, which will occur this fall, we will extract RNA and measure GnRH gene expression in these animals. The results of these studies will determine whether the environmental toxicants affect GnRH mRNA levels, thereby clarifying some of the mechanisms by which these substances may act to influence reproductive development.
Supplemental Keywords:RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Toxics, ENVIRONMENTAL MANAGEMENT, HUMAN HEALTH, Environmental Chemistry, Health Risk Assessment, Exposure, Epidemiology, pesticides, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Biochemistry, Physical Processes, Children's Health, genetic susceptability, Risk Assessment, health effects, pesticide exposure, sensitive populations, health risks, PCBs, biological response, neurodevelopment, children, Human Health Risk Assessment, neurotoxicity, human exposure, pesticide residues, assessment of exposure, growth and development, neurodevelopmental toxicity, exposure pathways, harmful environmental agents, environmental health hazard, dietary exposure, growth & development, developmental disorders, exposure assessment, neurological development
Progress and Final Reports:Original Abstract
Main Center Abstract and Reports:R827039 Mount Sinai Center for Children's Environmental Health and Disease Prevention Research
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R827039C001 Growing Up Healthy in East Harlem
R827039C002 Exposure to Indoor Pesticides and PCBs and their Effects on Growth and Neurodevelopment in Urban Children
R827039C003 Genetics of Chlorpyrifos Risk in Minority Populations
R827039C004 Prenatal PCB Exposure and Neurodevelopmental Outcomes in Adolescence and Adulthood
R827039C005 Neuroendocrine Mechanisms of Environmental Toxicants: PCBs and Pesticides