In Utero Lead Exposure: Fetal Epigenetics and Life-Course Physiologic EffectsEPA Grant Number: R834800C001
Subproject: this is subproject number 001 , established and managed by the Center Director under grant R834800
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Perinatal Exposures, Epigenetics, Child Obesity and Sexual Maturation - University of Michigan
Center Director: Peterson, Karen E.
Title: In Utero Lead Exposure: Fetal Epigenetics and Life-Course Physiologic Effects
Investigators: Peterson, Karen E.
Institution: University of Michigan
EPA Project Officer: Hahn, Intaek
Project Period: August 9, 2010 through August 8, 2013
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
Epidemiological studies and animal experiments have now firmly established that environmental exposures during early embryonic development play a critical role in disease susceptibility in later life. Moreover, such exposures during gestation have been directly linked with subsequent disease formation through epigenetic mechanisms, or the ways genes are regulated and controlled. Relatively little research, however, has considered the mechanisms by which perinatal environmental exposures may influence physical growth and development during sensitive periods in early and mid-childhood. Using lead (Pb) as a representative maternal toxicant, this pilot project focuses on the influence of in utero exposures on a child’s body composition, hormonal status, and epigenetic gene regulation. Specifically, we will investigate the hypothesis that early exposure to Pb results in dose-dependent epigenetic alterations in critical DNA control elements and influences physiologic status throughout life. First, using the viable yellow agouti (Avy) mouse, we will develop a model of dose-dependent material Pb effects on the fetal epigenome. We will evaluate changes in Avy/a offspring coat color phenotype and DNA methylation at metastable and imprinted loci following maternal exposure to water containing low (27 ppm) and moderate (55 ppm) lead levels. Second, we will examine the relationship of prenatal Pb exposure to physiological parameters (whole body composition, spontaneous activity, and food intake) and hormonal status (leptin and IGF-1) throughout the life-course.
Knowledge generated from the proposed studies is crucial for deciphering the role of early epigenetic (DNA gene expression) programming in the pathogenesis of disease and for the development of novel epigenetic-based diagnostic, screening, and therapeutic strategies for human diseases and disorders.
Supplemental Keywords:HUMAN HEALTH,INTERNATIONAL COOPERATION,Scientific Discipline,Health,RFA,Biology,Children's Health,Environmental Policy,Exposure,developmental disorders,perinatal exposure,dietary factors,children's environmental health,childhood obesity,assessment of exposure,age-related differences,genetic susceptibility,epigenetics,dietary exposure,abnormal sexual maturation,biological response,environmental risks, RFA, Health, Scientific Discipline, INTERNATIONAL COOPERATION, HUMAN HEALTH, Exposure, Children's Health, Environmental Policy, Biology, abnormal sexual maturation, age-related differences, environmental risks, perinatal exposure, biological response, epigenetics, childhood obesity, assessment of exposure, children's environmental health, dietary exposure, dietary factors, developmental disorders
Progress and Final Reports:
Main Center Abstract and Reports:R834800 Perinatal Exposures, Epigenetics, Child Obesity and Sexual Maturation - University of Michigan
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834800C001 In Utero Lead Exposure: Fetal Epigenetics and Life-Course Physiologic Effects
R834800C002 Impacts of Life-stage Exposures to BPA and Phthalates on Growth and Development