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Mechanisms of In Utero BPA Exposure on Fetal Gonad DevelopmentEPA Grant Number: R834593C003
Subproject: this is subproject number 003 , established and managed by the Center Director under grant R834593
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Novel Methods to Assess Effects of Bisphenol A & Phthalates on Child Development
Center Director: Schantz, Susan L.
Title: Mechanisms of In Utero BPA Exposure on Fetal Gonad Development
Investigators: Schantz, Susan L.
Institution: University of Illinois at Urbana-Champaign , Harvard T.H. Chan School of Public Health , Michigan State University
EPA Project Officer: Louie, Nica
Project Period: February 15, 2010 through February 14, 2014
RFA: Children's Environmental Health and Disease Prevention Research Centers: Formative Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Health
The main objective of this research project is to understand how in utero Bisphenol A (BPA) exposure affects fetal gonadal development and reproduction in adulthood in mice. In utero exposure to estrogenic endocrine disruptors such as diethylsfilbestrol (DES) is known to cause sex organ malformation, reproductive carcinogenesis, and fertility defects in both male and female in humans and rodents. Based on DES studies, it is proposed that in utero exposure to other endocrine disruptors, particularly those that work through estrogen receptors, may lead to reproductive diseases in adulthood. BPA, a chemical used in synthesis of plastics, exhibits estrogenic activities and deleterious effects on reproduction when given to adult rodents. BPA is detected in serum of pregnant women, umbilical cord blood, and fetal plasma, indicating that developing fetuses are exposed to BPA. Although effects of BPA on adult reproductive organs have been studied extensively, impacts of in utero BPA exposure particularly on fetal gonadal development are not well understood. In vitro experiments have suggested that BPA, similar to other estrogenic compounds, could bind to classical nuclear estrogen receptors (ERa or p), which are present in fetal mouse gonads. Therefore, the main goal of this Research Project is to test the hypothesis that in utero exposure to BPA causes gonadal defects in fetal and adult life via ERs. We design two specific aims to 1) investigate whether loss of ERa or |3 in fetal gonads render embryos insensitive to deleterious effects of BPA in reproductive functions and 2) study whether over expression of ER increases the susceptibility of embryos to in utero exposure of BPA. The proposed experiments take advantage of the power of transgenic mouse models in combination of classic toxicological approaches.
This project will not only provide animal models to test hypotheses that human models cannot, but also complementary information to interpret results of other components of the formative grant.
Supplemental Keywords:health effects, sensitive populations, genetic polymorphisms, epidemiology,, RFA, Health, Scientific Discipline, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Biochemistry, Children's Health, children's vulnerablity, biological markers, developmental disorders
Main Center Abstract and Reports:R834593 Novel Methods to Assess Effects of Bisphenol A & Phthalates on Child Development
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834593C001 Prenatal Exposure to BPA/Phthalates: Infant Physical and Behavioral Development
R834593C002 Adolescent Exposure to BPA/Phthalates Cognitive and Behavioral Development
R834593C003 Mechanisms of In Utero BPA Exposure on Fetal Gonad Development
R834593C004 Effects of Bisphenol A on the Developing Cortex