Parent Title:
Perinatal Exposures, Epigenetics, Child Obesity & Sexual Maturation
Grant Number:
Principal Investigator:
Peterson, Karen
Institution:
University of Michigan
Most Recent Award Year:
2010
Lifestage of Participants:
Exposure:
Prenatal
Assessment:
Youth (1-18 years)
Exposures:
Metals:
Lead
Health Outcomes:
Metabolic Outcomes:
Obesity/body weight
Reproductive Outcomes:
Premature/delayed puberty
Biological Sample:
Cord blood
Other Participant Data:
Maternal bone lead
Genes or Other DNA Products Studied:
Genes associated with early growth (e.g., imprinted loci IGF2 and HI 9; non-imprinted genes IGF2R and 11ss-HSD)
Epigenetic Mechanisms Studied:
DNA methylation
Abstract:
The 'early origins' hypothesis postulates that environmental factors influence plasticity during the perinatal period, altering susceptibility to adult chronic diseases. This emerging field of research points to the epigenome as a modifier of disease susceptibility. Less is known about mechanisms by which adverse exposures in utero may affect physical growth and development during sensitive periods in early and mid-childhood. Among these outcomes, child weight gain and weight status and the tempo of maturation can increase the risk of adult diseases, e.g., diabetes, obesity, cardiovascular disease, and some cancers. Interactions among a representative maternal toxicant, prenatal lead exposure, child growth and epigenetic mechanisms nevertheless remain largely unexplored. Our preliminary studies suggest that the epigenome of the developing fetus can be affected by maternal cumulative lead burden and may influence long-term epigenetic programming. This research project capitalizes on synergies among epigenetics, environmental health and nutrition newly available at the University of Michigan School of Public Health and strengths of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) research collaboration with Mexico's Instituto Nacional de Salud Publica. Longitudinal data on ELEMENT cohorts and new information on physical and hormonal biomarkers of adolescent development will be used to describe the relationship of prenatal lead exposure, assessed by maternal bone lead, to child weight gain and status and to sexual maturation among 200 youth aged 8-17 yr. Examining whether prenatal lead exposure affects cord blood DNA methylation levels in four key genes associated with early growth (imprinted loci IGF2 and HI 9; non-imprinted genes IGF2R and 11ss-HSD) will support consideration of DNA methylation as a mediator the associations of early lead exposure with growth and development. Using prenatal lead exposure as a representative maternal toxicant, this longitudinal study and a P20 pilot study in animals can provide invaluable insights into epigenetic regulation of early exposures affecting childhood health outcomes that confer long term disease risk. The recent emergence of the epigenome as a modifier of perinatal environmental exposures offers a unique opportunity to understand mechanisms that alter susceptibility to adult chronic diseases. This study will yield insights into interactions among in utero exposure to a representative maternal toxicant (bone lead), child growth & maturation and epigenetic mechanisms that confer long-term disease risk.
ExpandCollapse Abstract
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.