Grant Number:
Principal Investigator:
Baccarelli, Andrea; Wright, Robert O (Contact)
Institution:
Mount Sinai School of Medicine
Most Recent Award Year:
2011
Lifestage of Participants:
Exposure:
Prenatal; Adulthood (mother)
Assessment:
Infant (0-1 year)
Exposures:
Air Pollutants:
Tobacco smoke
Metals:
Lead
Non-Chemical Stress:
Psychosocial stress
Health Outcomes:
Birth Outcomes:
Birthweight
Biological Sample:
Cord blood; Placenta
Epigenetic Mechanisms Studied:
DNA methylation in target tissues critical for fetal growth
Abstract:
Previous studies on impaired fetal growth have identified multiple risk factors including environmental tobacco smoke (ETS), social stress, lead exposure and air pollution. In parallel, a growing body of literature has demonstrated that all 4 of these risk factors can alter DNA methylation, suggesting a common pathway by which such environmental factors impair fetal growth. The key to understanding the role of environment in impairing fetal growth is to 1) measure environmental risk factors prospectively in pregnancy, to ensure that exposure and subsequent epigenetic changes are temporally associated and 2) to measure epigenetic changes in the correct target tissues. While a case control design may be more efficient, such a design could not tease out whether methylation changes were due to environmental factors or were constitutive in impaired growth. This point is critical as reducing risk by intervening on environmental factors requires knowledge of their mechanisms. To this end, this proposal will utilize the existing infrastructure of the ELEMENT birth cohort study in Mexico and a second ongoing study of similar design in Boston-PRISM. ELEMENT and PRISM have archived umbilical cord vessels and placenta as well as ETS, stress, air pollution and lead exposure measured prospectively beginning in the early 2nd trimester and data on fetal growth. We are therefore uniquely positioned to address these important questions. In this proposal, we hypothesize that common environmental risk factors that impair fetal growth will alter methylomic marks in target tissues critical for fetal growth. Fetal growth depends on maternal transport of nutrients as well as the transport and excretion of toxicants and waste products. Logical target tissues for fetal growth would be tissues of the vascular system (vessels, blood and placenta). Perhaps the greatest strength of our proposal is that we can assess multiple "target tissues" and can compare and contrast 450,000 unique methylation sites across these tissues in the context of environmental exposures. This study will make substantial contributions to our understanding the role of environment in fetal growth.
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Related NIEHS-Funded Study Populations
Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT)
Principal Investigator:
Hu, Howard; Peterson, Karen; Hernandez-Avila, Mauricio; Tellez-Rojo, Martha Maria
| Study Population Page Study Population c49
Institution:
University of Michigan
Location:
Mexico City, Mexico
Number of Participants::
1,653
Brief Description::
This is a group of three sequentially-enrolled, on-going, epidemiologic birth cohort studies in Mexico City with an original aim to investigate the impact of lead on child development. The research aims have since expanded to include a wide range health outcomes and environmental, nutritional, behavioral, genetic, and epigenetic risk factors. More than 1,600 mother-child pairs enrolled in the study beginning in 1994, some of whom have been followed for over two decades.