2012 Progress Report: Perinatal Exposures, Epigenetics, Child Obesity & Sexual Maturation

EPA Grant Number: R834800
Center: Perinatal Exposures, Epigenetics, Child Obesity and Sexual Maturation - University of Michigan
Center Director: Peterson, Karen E.
Title: Perinatal Exposures, Epigenetics, Child Obesity & Sexual Maturation
Investigators: Peterson, Karen E. , Meeker, John D. , Dolinoy, Dana
Institution: University of Michigan
EPA Project Officer: Hahn, Intaek
Project Period: August 9, 2010 through August 8, 2014
Project Period Covered by this Report: April 1, 2011 through March 31,2012
Project Amount: $1,335,311
RFA: Children's Environmental Health and Disease Prevention Research Centers: Formative Centers (with NIEHS) (2009) RFA Text |  Recipients Lists
Research Category: Children's Health , Human Health

Objective:

Center Objectives
 
Overweight and obesity in children has increased significantly over the past few decades. Many attempts have been made to reverse this trend through school food reforms, clinical counseling of at risk youth, camps and group clinics that focus on lifestyle and behavior change. However, CEHC research offers a new perspective on the childhood obesity dilemma. Recent environmental health research suggests that early life exposure to environmental toxins, such as lead, bisphenol A, and phthalates, which we are studying at the UM-CEHC, also may affect child growth trajectories, body mass index (BMI), and the tempo of sexual maturation.
 
If an association between in utero or early life exposure to lead, bisphenol A, or phthalates with child growth, development, and/or sexual maturation, is demonstrated, this information can be used to inform future policies for decreasing exposure to substances related to obesity and the multitude of associated co-morbidities. Knowledge of environmental exposures that are associated with adverse health effects also can be used by physicians, public health workers, and community activists to educate the general public about ways to avoid these exposures.
 
The specific aims of this Center are to:
1.    Characterize the effect of lead, bisphenol A, and phthalates on weight gain and status (BMI) and the development of obesity in early/mid childhood and on pubertal timing assessed by Tanner staging and hormonal biomarkers.
2.    Utilizing lead as a model toxicant, examine the epigenetic mechanisms, e.g., DNA methylation of four key growth-regulating genes, associated with perinatal exposure and potential modification of the development of obesity and pubertal timing.
3.    Enhance career development by assisting new investigators and trainees in the advancement of their research skills and knowledge in translational and children’s environmental health research.
4.    Involve key stakeholders in Michigan and Mexico via a Community Engagement Plan aimed to educate and inform study participants, policy makers and public health decision makers on children’s environmental health exposures of concern.
5.    Apply research findings, infrastructure, and partnerships gained through the Formative P20 Center to the development of a full P01 Children’s Environmental Health Center at the University of Michigan.
 
Research Project Objectives
 
Cross-sectional studies suggest that low-level lead exposure is associated with physician observed onset of puberty in boys and girls, delayed age of self-reported menarche in girls and marginally reduced testicular volume in boys. Prenatal lead exposure among rats has been shown to cause a decrease in several puberty-related hormones. Lead is consistently associated with decreased birth and infant length, which continues into early childhood as stature decrement; however the association between lead exposure and child weight status is less consistent. This project is primed to address both the question of lead’s effect on child weight status and tempo of sexual maturation. Preliminary studies suggest that maternal lead measures are inversely associated with umbilical cord DNA methylation. Epigenetic fetal programming via DNA methylation may provide a pathway for lead exposure to influence disease susceptibility. The analysis of umbilical cord DNA methylation in Research Project subjects will provide valuable insight into a possible association between prenatal lead exposure and childhood weight gain and weight status.
 
The specific aims of this Research Project are to:
1.       Describe the relationship of prenatal lead exposure to sexual maturation.
2.       Describe the association of prenatal lead exposure with childhood weight gain and status.
3.       Examine the relationship of prenatal lead exposure to cord blood DNA methylation levels in four genes associated with early growth.
 
 
Pilot Project 1 Objectives
 
Using lead and BPA as representative environmental toxicants, a mouse model of dose-dependent epigenetic and life-course physiological assessment will strengthen children’s health risk assessment and shape diagnostic and therapeutic strategies. First, the identification of epigenetic exposure biomarkers will be useful in the identification of at-risk individuals prior to disease onset. Second, unlike genetic mutations, epigenetic profiles are potentially reversible. Therefore, epigenetic approaches for prevention and treatment, such as nutritional supplementation or pharmaceutical therapy, may be developed to counteract negative epigenomic profiles. For example, if we determine that lead exposure results in hypomethylation and increased incidence of yellow Avy/a offspring, it would be important to determine if nutritional supplements (e.g., folic acid and genistein) not only during development, but also later in life can protect against these negative effects on the epigenome. Therefore, the future of epigenomics holds tremendous potential not only for individualized children’s health, but also for population-wide disease diagnostic, screening, and prevention strategies.
 
The specific aims of this Pilot Project are to:
  1. Develop a mouse model of dose-dependent maternal lead effects on the fetal epigenome.
  2. Examine the relationship of prenatal lead exposure to physiological parameters and hormonal status throughout the life-course.
 
Pilot Project 2 Objectives
 
Human exposure to phthalates and bisphenol A are widespread, so the public health significance for Pilot Project 2 is potentially huge. The health effects of this exposure may be amplified by the sensitive developmental windows being assessed in the study. In the meantime, the analysis being conducted using NHANES and other data sources also could have large impacts in helping us understand human exposure to these compounds and their related health effects.
 
The specific aims of Pilot Project 2 are to:
  1. Compare urinary concentrations of BPA and phthalate metabolites from pregnant women and adolescents in Mexico City with those measured in the U.S. general population.
  2. Explore the association between BPA and phthalate exposure and birth outcomes.
  3. Investigate the relationship between early life (in utero) exposure to BPA and phthalates and measures of weight, body mass index, growth in infancy and early childhood.
  4. Explore the association between exposure to BPA and phthalates in early life (in utero) and in adolescence with stages of sexual maturation and relevant endocrine markers in Mexican youth.
  5. Determine predictors of BPA and phthalate exposure among adolescents in Mexico City.

 

Progress Summary:

Center Progress to Date
 
Progress and plans related to Aims 1 and 2 are described separately for the Research Project and the two Pilot Projects.
 
Research Project Progress to Date
 
The following Research Project tasks were completed this year:
  • INSP field study staff in Mexico were hired, trained, and standardized for study-specific questionnaires and measures, including a 3-day anthropometry and Tanner staging intensive course with study consultant, Dr. Jorge Chavarro.
  • Recruitment began in September 2011 with more than 100 participant visits completed in Year 2.
  • Hormone analyses of the first 53 study participants were completed in December 2011; analyses for an additional 56 participants are under way.
  • Assay design for candidate gene methylation at key growth related genes was completed.
  • Archived DNA samples (n=390) from ELEMENT cohorts, from which UM-CEHC participants are being recruited, were identified. DNA was bisulfite converted and pyrosequencing of four candidate genes (IGF-1, H19, IGF2R, 11ss-HSD2) is complete for the first 300 samples.
  • Archived cord blood samples (n=203), from the UM-CEHC recruitment pool of ELEMENT cohort participants, were identified. Bisulfite conversion and pyrosequencing of these samples will occur over the next 3 months, in conjunction with current DNA collected during study visits.
  • Complete study data for the first 109 participants were transmitted via secure internet connection from the field study location in Mexico City to investigators at the UM-SPH.
  • Data cleaning and initial analyses have begun with data from the first 109 participants.
 
The following Research Project findings were published or presented this year:
  • Prenatal lead exposure, assessed by maternal patella lead measured 1-month postpartum, is associated with a significantly lower weight in female children by age 5. Prenatal lead exposure non-significantly increased male children’s weight at 5 years of age. This is the first longitudinal study to investigate the association of cumulative prenatal lead exposure on children’s weight trajectory between birth and 5 years. (Afeiche, EHP 2011)
  • Assessing lead exposure at three developmental periods: prenatal, infancy and early childhood, children with higher than median blood lead levels during infancy are significantly shorter at 48 months than children with blood lead levels below the median, suggesting infancy as the window of greatest sensitivity to lead exposure. Increased lead exposure trended, non-significantly, to lower BMI. (Afeiche, J Pediatr 2012)
  • Increases in concurrent, maternal BMI are associated with higher BMI in children, aged 7-15 years, and with greater waist circumferences in both boys and girls. Prenatal lead exposure, assessed by maternal patella lead at 1-month postpartum, is associated with significantly lower BMI in preadolescent and adolescent girls. No association is observed between prenatal lead exposure and BMI in boys. (Peterson,ISEE 2011 poster)
  • Maternal patella lead is not associated with odds of earlier or later onset of puberty. However, a 1 μg/g increase in maternal patella lead was associated with non-significant odds of earlier breast development in girls. (Afeiche, manuscript).
Pilot Project 1 Progress to Date
 
Progress is described by Specific Aim below.
 
Specific Aim 1:
The following Pilot Project 1 tasks related to Specific Aim 1 were completed this year:
  • Maternal lead exposure in the viable yellow agouti mouse model began in the summer of 2011 with exposure via water: control (0 ppm lead) and three exposure groups (3.7 ppm, 27 ppm, or 55 ppm). Water used for control animals and to make stock lead solutions was sent to NSF International (Ann Arbor, MI) for objective verification of lead-free water content. For further quality control, lead stock solutions also were sent to NSF International for verification of expected lead levels; minor adjustments were subsequently made to solutions to attain the desired lead levels.
  • Animal colony expansion for this study began in late 2010. Six control litters, eight low (3.7 ppm) dose, eight medium (27 ppm) dose, and eight high (55 ppm) dose litters are currently included in the study. An additional four to six litters per group are planned over the next 4 months.
  • DNA methylation assays for the Avy and Cabp metastable alleles have been conducted on all study animals. Candidate genes assay design is being optimized for the remaining candidate genes (IGF2, H19, IGF2R).
Preliminary analysis of Pilot Project 1 findings suggest:
 
  • Statistically significant shifts in the coat color distribution of the viable yellow agouti mice toward the yellow phenotype in both the medium and high lead dose groups compared to controls. This suggests that maternal exposure to lead at these doses decreases DNA methylation at the Avy allele, an established biosensor for maternal exposure and offspring epigenetic effects.
  • DNA methylation at both Avy and Cabp is decreased in the medium and high lead exposure groups compared to control offspring.
 
Specific Aim 2:
The following Pilot Project 1 tasks related to Specific Aim 2 were completed this year:
  • Lean Avy offspring (a/a genotype only) began life-course evaluations of body composition, spontaneous activity, energy expenditure and food intake at the Michigan Metabolomics and Obesity Center, Animal Phenotyping Core this past year. These evaluations occur at three time points throughout life (3, 6, and 9 months).
  • Pilot funds from the Michigan Nutrition and Obesity Research Center (NORC, NIH DK089503) were received in 2010 to conduct these physiological, hormonal, and epigenetic studies following dose-dependent maternal exposure to BPA, a chemical of interest in the UM-CEHC. In utero exposure to BPA via maternal diet at 50 ng (n=20), 50 μg (n=21), or 50 mg (n=18) and analysis at all three time points are complete in these mice.
Preliminary analysis of Pilot Project 1 findings suggest:
  • Life-course analysis of BPA-exposed mice indicates in utero BPA exposure is associated with hyperactive and possibly lean phenotypes based on the following significant differences between mice exposed to 50 mg BPA vs. controls: increased oxygen consumption (males at 3 months, females at 9 months), higher carbon dioxide production (females at 6 months), increased vertical activity (3 months in males, 3 and 9 months in females), increased ambulatory activity (females at 9 months). Female offspring exposed to 50 ng and 50 μg BPA in utero displayed marginally significant decreases in body weight and percent body fat. These findings make it necessary to further evaluate BPA as a potential human obesogen.
 
Pilot Project 2 Progress to Date
 
The following Pilot Project 2 tasks were completed this year:
  • All Pilot Project 2 aims depend on human participant recruitment, which is progressing ahead of schedule (see Research Project).
  • A product-use and activity questionnaire to predict BPA and phthalate concentrations was developed for this Mexican cohort. The questionnaire was shared with collaborators at INSP, translated into Spanish, and approved by the Institutional Review Boards at both institutions.
  • A full inventory of archived maternal urine samples from pregnancy in the ELEMENT study available for measurement of BPA and phthalates has been conducted. This inventory provided crucial input for UM-CEHC recruitment; assessment of BPA and phthalate exposures both in utero and at current levels is important to developmental outcomes of interest.
  • The relationship between the UM-CEHC and NSF International strengthened over the past year. This partnership provides both current state-of-the-art and cost-efficient laboratory support and a foundation for future collaborations. Pilot Project 2 personnel worked with NSF chemists to develop and validate the methods for BPA and phthalate analysis.
  • Urine specimens from the first 50 UM-CEHC participants and a matched, archived sample of maternal urine from pregnancy when the child was in utero currently are being analyzed at NSF International.
The following research findings related to Pilot Project 2 were published or presented this year:
  • In an analysis of recent NHANES data, multiple phthalate metabolites were significantly, positively associated with common markers of inflammation (C-reactive protein) and oxidative stress (gamma glutamyltransferase). (Ferguson, Environ Res 2011)
  • A follow-up, exploratory analysis revisited the association between phthalate exposure, inflammation, and oxidative stress, using less common biomarkers thought to be part of the causal pathway between phthalates and adverse developmental impacts. Stronger associations between these less-used biomarkers compared to common markers suggest they may be more sensitive indicators of the process by which environmental exposure to phthalates may alter thyroid signaling. (Ferguson, Environ Sci Technol 2012)
  • A number of significant relationships were observed between phthalates and serum thyroid hormone levels in another NHANES analysis, suggesting that phthalates may impact thyroid signaling. These results were widely covered in the mainstream news media and a podcast was recorded and made available online [http://ns.umich.edu/new/multimedia/audio/10333-new-health-concerns-with-bpa]. (Meeker, EHP 2011)
All the aims in Pilot Project 2 rely on the recruitment of participants, so in order to prepare for participant recruitment, we have:
  • Conducted a full inventory of archived maternal urine samples from pregnancy in the ELEMENT study available for measurement of BPA and phthalates.
  • Strengthened our relationship with NSF International (headquartered in Ann Arbor, MI), which will provide state-of-the-art and cost-efficient laboratory support for measuring biomarkers of BPA, phthalates, and other agents in the future. This step will assure data quality.
  • Developed a product-use and activity questionnaire for this Mexico cohort for use in the investigation of factors that may predict BPA and phthalate concentrations in the samples collected at re-recruitment. The questionnaire has been shared with our Mexico collaborators, translated into Spanish, and approved by the Institutional Review Boards at both institutions.
  • Finalized the list of analytes (e.g., hormone levels) to measure in blood, and locate laboratories to conduct the measurements used for this Pilot and the Research Project.

Career Development

Our institutional commitment to career development is reflected in the Center leadership and organizational structure:  both Pilot Project PIs (Dr. Dolinoy and Dr. Meeker) and the Leader of the Environmental Biostatistics Core (Dr. Sanchez) are New Investigators. These new investigators were all Assistant Professors at the time the grant began.

  • John Meeker, Sc.D. was promoted with tenure to Associate Professor in July 2011. In November 2011, he was appointed Associate Chair of the Department of EHS at UM-SPH.
  • Dana Dolinoy, Ph.D. received the Norman Kretchmer Memorial Award from the American Society for Nutrition (ASN) and the Classic Paper of the Year Award from Environmental Health Perspectives for Dolinoy et al. 2006. “Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome,” the most cited paper in the journal in the past 5-year cycle. She was an invited participant in the NIEHS Strategic Vision Stakeholder Workshop, Durham, North Carolina, July 2011 and will be presenting at a September 2011 session of The Obesity Society as a session on ‘Environmental Obesogens’.
  • Brisa Sanchez, Ph.D. has been invited to serve on a National Research Council committee examining the effects of repeated lead exposure on Department of Defense firing personnel. She was also awarded a Robert Wood Johnson Foundation grant to develop methodologies to study geographical variations in prevalence and prevalence trends of childhood obesity, and potential environmental contributors.
  • Joyce Lee, M.D., M.P.H. received a joint appointment in the Human Nutrition Program in the UM-SPH Department of EHS as an Assistant Professor. She is in the process of promotion to Associate Professor of Pediatrics in the University of Michigan Medical School and Dr. Lee serves as faculty mentor for a Pediatric Endocrinology Fellow.

The UM-CEHC includes four pre-doctoral students. Doctoral and post-doctoral students participate in bi-monthly Center meetings and present their ongoing analyses in multiple venues including an EHS doctoral seminar course, the EHS-Human Nutrition Program doctoral journal club, and the University of Michigan Environmental Molecular Epidemiology Research Group (EMERG) workgroup weekly meetings.

Three post-doctoral fellows now play an integral role in the UM-CEHC:

  • Christopher Faulk, Ph.D., who oversees Pilot Project 1 has been invited to present Center research at the Sixth International Conference on Environmental Mutagens in Doha, Qatar, march 26-28, 2012.
  • Jaclyn Goodrich, Ph.D. joined the UM-CEHC team this year and brings a background in gene-environment interactions with a specific focus on metals and endocrine active compounds.
  • Sunghee Lee, Ph.D., who is investigating the association between dietary patterns during pregnancy and post-partum weight retention among ELEMENT mothers, also joined the UM-CEHC team this year.

Community Engagement

  • A brochure on the dangers of lead exposure and ways to avoid it is being revised to be relevant to the Mexican American community in Southwest Detroit. The informational brochure was developed and distributed to study participants, with our collaborators at the Instituto Nacional de Salud Publica (INSP) in Mexico in Year 1.   
  • UM-CEHC researchers have started to work with a new community group, the Community Health and Social Services (CHASS) Center in the largely Mexican-American community in Southwest Detroit. This new connection expands the reach of Center outreach activities in the United States.
  • The UM-CEHC website (http://www.sitemaker.umich.edu/cehc/) is being updated to provide information in Spanish (in addition to the English text already provided). Updates will present UM-CEHC research findings in a clear, concise way, addressing the values of potential audiences.
  • In June 2011, a meeting between UM-CEHC investigators and a pediatric neurologist at ABC Hospital in Mexico City strengthened connections with the hospital, which is interested in contributing to future research relating prenatal and early childhood environmental exposures to neurologic and metabolic health outcomes in children. This will provide access to more sophisticated diagnostic facilities and clinical space for future children’s environmental health collaborations between UM-CEHC investigators and ABC Hospital physicians.
  • A June 2011 meeting with Dr. Simon Barquera, Director of Nutritional Epidemiology, Center for Research in Nutrition and Health, INSP, Mexico, began discussions of optimal communication and translation of UM-CEHC findings into a policy context in Mexico. Collaboration with Dr. Barquera provides access to Mexican nutrition policy measures through INSP and La Secretaría de Salud.
  • The UM-CEHC co-sponsored a speaker at the UM Department of Environmental Health Sciences 17th Annual Toxicology and Epidemiology Symposium, ‘Nutrient-Toxicant Interactions: Bridging the Gap Between Diet and Environment.’ Dr. Emily Oken, Department of Population Medicine, Harvard Medical School gave a presentation entitled ‘Which fish should I eat? Perspectives influencing fish consumption choices,’ which discussed the paradox of beneficial nutritional properties and detrimental health impacts of environmental contamination in fish.
Administrative Core
 
  • Bi-monthly meetings and conference calls between Center investigators at different study site locations continued throughout Year 2, providing regular opportunities to discuss resource utilization and optimization to facilitate efficient implementation of improvements.
  • A grant to the University of Michigan Office of the Vice President of Research was submitted in September 2011 (now awaiting fund allocation) to support the development and technical support of customized sample tracking software, which will increase quality control for biological specimens and will provide a foundation for a readily accessible bio-repository.
  • An annual internal audit by the UM-CEHC Quality Assurance Manager will be completed the second week of April 2012. The audit will review UM-CEHC methods and practices to ensure they meet standards set by the Quality Management Plan.

Environmental Biostatistics Core

  • A Data Management Plan (DMP) was written by UM-CEHC investigators in Michigan and Mexico to streamline secure data sharing between these UM-CEHC study locations. The DMP has simplified data sharing and made data transfers quicker and more efficient.
  • Study consultant, Dr. Jorge Chavarro, conducted a formal standardization of measurement methods for anthropometric and maturation outcomes in June 2011. Both group and individual training were included.
  • New collaborations with U-M Biostatistics faculty, Peter Song, Ph.D. and Naisyin Yang, Ph.D., have been initiated to develop advanced approaches to modeling physical growth during sensitive periods of development.

Future Activities:

Center Future Activities
 
Project-specific plans for Year 2 are detailed below with descriptions of each Project.
 
Research Project Future Activities
 
  • Study recruitment continues as a UM-CEHC priority; recruitment completion is expected in the summer of 2012.
  • DNA methylation analysis of candidate genes in archived, cord blood DNA and DNA from current blood samples will be completed in Year 3.
  • Hormone analyses in current blood samples will be completed in Year 3.
  • Data analysis will become an increasing priority in Year 3 as an emphasis on manuscript preparation and publication increases over the next year.
  • Submission of an R21 investigating the long-term metabolic consequences of environmental exposures (to lead, BPA, and phthalates) during the pregnancy for both the mother and adolescent offspring is awaiting funding. This project will build on the UM-CEHC by re-recruiting participants to investigate the impact of perinatal exposures on (1) hyperglycemia during pregnancy, (2) markers of insulin resistance and metabolic syndrome in adolescents.
Pilot Project 1 Future Activities
 
  • In utero lead exposure is expected to be complete by the fall of 2012.
  • Epigenetic analysis of candidate genes will be completed in Year 3.
  • Metabolic assessments of a/a offspring at 3, 6, and 9 months will continue into Year 3. Hormone levels in plasma collected at day 22 and 10 months will be analyzed. A 5-hour fasting glucose tolerance test to measure insulin sensitivity has been added to the original proposal at the 9-month assessment.
  • Animals exposed in utero to BPA will be assessed for BPA-induced epigenetic changes via promoter tiling arrays with funding from the NORC pilot grant. Epigenetic results will be analyzed in combination with metabolic parameters to determine if epigenetic mechanisms mediate the effects of BPA exposure on measured phenotypes.
  • Additional Pilot Funds from the UM P30 NIEHS Core Center were obtained to utilize brain tissue from the lead-exposed mice in the UM-CEHC Pilot Project 1. Frontal cortex tissues from 10-month old, sacrificed mice will be separated into neuronal nuclei and non-neuronal nuclei. Differential DNA methylation in the neuronal cell population compared to non-neuronal cells globally and in the promoter regions of four candidate genes (Adam17, Bace1, Aph1a, Drd1a) are expected. Methylation levels as well as spontaneous activity levels are expected to differ in lead-exposed compared to non-exposed mice. This is the first neuron-specific environmental epigenetics study conducted in any species and will contribute to the field of cell-type specific epigenetics.
Pilot Project 2 Future Activities
 
  • Urine analysis for BPA and phthalate exposure will continue in Year 3, on current samples collected from UM-CEHC study participants and archived maternal urine samples from pregnancy.
  • Data analysis for Pilot Project 2 aims is beginning and will continue throughout Year 3.
  • With the completion of recruitment expected in the summer of 2012, final data analysis and manuscript preparation will be a focus in the second half of Year 3. Related analyses and papers are ongoing as UM-CEHC data are being generated.
Career Development
 
  • Monthly Center meetings that encourage participation and interactive brainstorming related to CEHC projects will continue to facilitate mentoring of junior faculty involved in the UM-CEHC.
  • Doctoral trainees whose work relates to Center Projects will continue to present their ongoing analyses at these monthly Center meetings and other Departmental venues.
Community Engagement
 
  • Continuing partnerships with the Detroit Hispanic Development Corporation (DHDC) and Community Health and Social Services (CHASS) Center aim to have targeted educational materials available to Detroit communities in the next 6 months.
  • Further engagement with Dr. Simon Barquera will facilitate translation of UM-CEHC research findings in a policy context in Mexico.
  • Stakeholder Advisory Group involvement will increase as plans for translation and dissemination of research findings to affected communities in Mexico City and Detroit are formalized.
Administrative Core
 
  • Funding for and implementation of a customized sample tracking and management software are expected in the beginning of Year 3, enabling improved quality control of current and archived human biospecimens. 
  • Communication with the Center’s External Advisory Committee will progress in the coming year.
Environmental Biostatistics Core
 
  • Dr. Brisa Sanchez will continue to create podcasts on environmental biostatistics topics and methods that relate to the UM-CEHC research.
  • Data analysis and database management will continue through Year 3. 


Journal Articles: 34 Displayed | Download in RIS Format

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Type Citation Sub Project Document Sources
Journal Article Afeiche M, Peterson KE, Sanchez BN, Cantonwine D, Lamadrid-Figueroa H, Schnaas L, Ettinger AS, Hernandez-Avila M, Hu H, Tellez-Rojo MM. Prenatal lead exposure and weight of 0- to 5-year-old children in Mexico City. Environmental Health Perspectives 2011;119(10):1436-1441.
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  • Journal Article Afeiche M, Peterson KE, Sanchez BN, Schnaas L, Cantonwine D, Ettinger AS, Solano-Gonzalez M, Hernandez-Avila M, Hu H, Tellez-Rojo MM. Windows of lead exposure sensitivity, attained height, and body mass index at 48 months. The Journal of Pediatrics 2012;160(6):1044-1049.
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  • Journal Article Anderson OS, Sant KE, Dolinoy DC. Nutrition and epigenetics:an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. The Journal of Nutritional Biochemistry 2012;23(8):853-859.
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  • Journal Article Anderson OS, Nahar MS, Faulk C, Jones T, Liao C, Kannan K, Weinhouse C, Rozek RS, Dolinoy DC. Epigenetic responses following maternal dietary exposure to physiologically relevant levels of bisphenol A. Environmental and Molecular Mutagenesis 2012;53(5):334-342.
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  • Journal Article Anderson OS, Peterson KE, Sanchez BN, Zhang Z, Mancuso P, Dolinoy DC. Perinatal bisphenol A exposure promotes hyperactivity, lean body composition, and hormonal responses across the murine life course. The FASEB Journal 2013;27(4):1784-1792.
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  • Journal Article Cantonwine D, Meeker JD, Hu H, Sanchez BN, Lamadrid-Figueroa H, Mercado-Garcia A, Fortenberry GZ, Calafat AM, Tellez-Rojo MM. Bisphenol A exposure in Mexico City and risk of prematurity:a pilot nested case control study. Environmental Health 2010;9:62.
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  • Journal Article Dolinoy DC, Faulk C. Introduction: the use of animals models to advance epigenetic science. ILAR Journal 2012;53(3-4):227-231.
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  • Journal Article Eng DS, Lee JM, Gebremariam A, Meeker JD, Peterson K, Padmanabhan V. Bisphenol A and chronic disease risk factors in US children. Pediatrics 2013;132(3):e637-e645.
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  • Journal Article Faulk C, Dolinoy DC. Timing is everything: the when and how of environmentally induced changes in the epigenome of animals. Epigenetics 2011;6(7):791-797.
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  • Journal Article Faulk C, Barks A, Dolinoy DC. Phylogenetic and DNA methylation analysis reveal novel regions of variable methylation in the mouse IAP class of transposons. BMC Genomics 2013;14:48.
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  • Journal Article Faulk C, Barks A, Liu K, Goodrich JM, Dolinoy DC. Early-life lead exposure results in dose- and sex-specific effects on weight and epigenetic gene regulation in weanling mice. Epigenomics 2013;5(5):487-500.
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  • Journal Article Faulk C, Barks A, Sanchez BN, Zhang Z, Anderson OS, Peterson KE, Dolinoy DC. Perinatal lead (Pb) exposure results in sex-specific effects on food intake, fat, weight, and insulin response across the murine life-course. PLoS One 2014;9(8):e104273.
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  • Journal Article Faulk C, Liu K, Barks A, Goodrich JM, Dolinoy DC. Longitudinal epigenetic drift in mice perinatally exposed to lead. Epigenetics 2014;9(7):934-941.
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  • Journal Article Ferguson KK, Loch-Caruso R, Meeker JD. Urinary phthalate metabolites in relation to biomarkers of inflammation and oxidative stress: NHANES 1999-2006. Environmental Research 2011;111(5):718-726.
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    R834800 (2011)
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  • Journal Article Ferguson KK, Loch-Caruso R, Meeker JD. Exploration of oxidative stress and inflammatory markers in relation to urinary phthalate metabolites: NHANES 1999-2006. Environmental Science & Technology 2012; 46(1):477-485.
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  • Journal Article Ferguson KK, Hauser R, Altshul L, Meeker JD. Serum concentrations of p,p’-DDE, HCB, PCBs and reproductive hormones among men of reproductive age. Reproductive Toxicology 2012;34(3):429-435.
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    R834800 (2013)
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  • Journal Article Ferguson KK, Peterson KE, Lee JM, Mercado-Garcia A, Blank-Goldenberg C, Tellez-Rojo MM, Meeker JD. Prenatal and peripubertal phthalates and bisphenol A in relation to sex hormones and puberty in boys. Reproductive Toxicology 2014;47:70-76.
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  • Journal Article Fortenberry GZ, Hu H, Turyk M, Barr DB, Meeker JD. Association between urinary 3,5,6-trichloro-2-pyridinol, a metabolite of chlorpyrifos and chlorpyrifos-methyl, and serum T4 and TSH in NHANES 1999-2002. Science of the Total Environment 2012;424:351-355.
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    R834800 (2013)
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  • Journal Article Fortenberry GZ, Meeker JD, Sanchez BN, Barr DB, Panuwet P, Bellinger D, Schnaas L, Solano-Gonzalez M, Ettinger AS, Hernandez-Avila M, Hu H, Tellez-Rojo MM. Urinary 3,5,6-trichloro-2-pyridinol (TCPY) in pregnant women from Mexico City:distribution, temporal variability, and relationship with child attention and hyperactivity. International Journal of Hygiene and Environmental Health 2014; 217(2-3):405-412.
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    R834800 (2013)
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  • Journal Article Goodrich JM, Sanchez BN, Dolinoy DC, Zhang Z, Hernandez-Avila M, Hu H, Peterson KE, Tellez-Rojo MM. Quality control and statistical modeling for environmental epigenetics: a study on in utero lead exposure and DNA methylation at birth. Epigenetics 2015;10(1):19-30.
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    R834800 (Final)
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  • Journal Article Koeppe ES, Ferguson KK, Colacino JA, Meeker JD. Relationship between urinary triclosan and paraben concentrations and serum thyroid measures in NHANES 2007-2008. Science of the Total Environment 2013;445-446:299-305.
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  • Journal Article Kordas K, Ettinger AS, Bellinger DC, Schnaas L, Téllez Rojo MM, Hernández-Avila M, Hu H, Wright RO. A dopamine receptor (DRD2) but not dopamine transporter (DAT1) gene polymorphism is associated with neurocognitive development of Mexican preschool children with lead exposure. The Journal of Pediatrics 2011;159(4):638-643.
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  • Journal Article Lamadrid-Figueroa H, Téllez-Rojo MM, Angeles G, Hernández-Ávila M, Hu H. Bias correction by use of errors-in-variables regression models in studies with K-X-ray fluorescence bone lead measurements.Environmental Research 2011;111(1):17-20.
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  • Journal Article Lewis RC, Meeker JD, Peterson KE, Lee JM, Pace GG, Cantoral A, Tellez-Rojo MM. Predictors of urinary bisphenol A and phthalate metabolite concentrations in Mexican children. Chemosphere 2013;93(10):2390-2398.
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  • Journal Article Meeker JD, Ferguson KK. Relationship between urinary phthalate and bisphenol A concentrations and serum thyroid measures in U.S. adults and adolescents from National Health and Nutrition Examination Survey (NHANES) 2007-2008. Environmental Health Perspectives 2011;119(10):1396-1402.
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  • Journal Article Meeker JD, Calafat AM, Hauser R. Urinary phthalate metabolites and their biotransformation products: predictors and temporal variability among men and women. Journal of Exposure Science and Environmental Epidemiology 2012; 22(4):376-386.
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  • Journal Article Meeker JD. Exposure to environmental endocrine disruptors and child development. Archives of Pediatrics and Adolescent Medicine 2012;166(6):E1-E7.
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  • Journal Article Meeker JD. Exposure to environmental endocrine disruptors and child development. Archives of Pediatrics and Adolescent Medicine 2012;166(10):952-958.
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  • Journal Article Rozek LS, Dolinoy DC, Sartor MA, Omenn GS. Epigenetics: relevance and implications for public health. Annual Review of Public Health 2014;35:105-122.
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  • Journal Article Sánchez BN, Hu H, Litman HJ, Téllez-Rojo MM. Statistical methods to study timing of vulnerability with sparsely sampled data on environmental toxicants. Environmental Health Perspectives 2011;119(3):409-415.
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  • Journal Article Tellez-Rojo MM, Cantoral A, Cantonwine DE, Schnaas L, Peterson K, Hu H, Meeker JD. Prenatal urinary phthalate metabolites levels and neurodevelopment in children at two and three years of age. Science of the Total Environment 2013;461-462:386-390.
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  • Journal Article Weinhouse C, Anderson OS, Bergin IL, Vandenbergh DJ, Gyekis JP, Dingman MA, Yang J, Dolinoy DC. Dose-dependent incidence of hepatic tumors in adult mice following perinatal exposure to bisphenol A. Environmental Health Perspectives 2014;122(5):485-491.
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  • Journal Article Wickerham EL, Lozoff B, Shao J, Kaciroti N, Xia Y, Meeker JD. Reduced birth weight in relation to pesticide mixtures detected in cord blood of full-term infants. Environment International 2012;47:80-85.
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    R834800 (2012)
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  • Journal Article Zhang A, Hu H, Sánchez BN, Ettinger AS, Park SK, Cantonwine D, Schnaas L, Wright RO, Lamadrid-Figueroa H, Tellez-Rojo MM. Association between prenatal lead exposure and blood pressure in children. Environmental Health Perspectives 2011;120(3):445-450.
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  • Supplemental Keywords:

    Children’s Health, Human Health, Health Effects, Children’s environmental health, prenatal exposure, environmental risks, exposure assessment, epigenetics, maternal exposure, Mexican, lead, bisphenol A, phthalates, animal exposure, agouti mouse, animal phenotyping, child weight, BMI, sexual maturation, children’s environmental health;, RFA, Health, Scientific Discipline, INTERNATIONAL COOPERATION, HUMAN HEALTH, Exposure, Biochemistry, Children's Health, Environmental Policy, Biology, abnormal sexual maturation, age-related differences, biological response, environmental risks, perinatal exposure, epigenetics, childhood obesity, assessment of exposure, children's environmental health, dietary exposure, dietary factors, developmental disorders

    Progress and Final Reports:

    Original Abstract
  • 2011 Progress Report
  • 2013 Progress Report
  • Final Report
  • 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