Grantee Research Project Results
2016 Progress Report: Lifecourse Exposures & Diet: Epigenetics, Maturation & Metabolic Syndrome
EPA Grant Number: R835436Center: Center for Research on Early Childhood Exposure and Development in Puerto Rico
Center Director: Alshawabkeh, Akram
Title: Lifecourse Exposures & Diet: Epigenetics, Maturation & Metabolic Syndrome
Investigators: Peterson, Karen E. , Padmanabhan, Vasantha
Institution: University of Michigan
EPA Project Officer: Hahn, Intaek
Project Period: June 1, 2013 through May 31, 2018 (Extended to May 31, 2019)
Project Period Covered by this Report: June 1, 2016 through May 31,2017
Project Amount: $3,651,990
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2012) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
The developmental origins hypothesis relates in utero exposures to endocrine disrupting chemicals (EDCs) to children’s physical growth and maturation and the later development of chronic diseases, including metabolic syndrome, a condition affecting up to 25% of U.S. adults and 30% of obese adolescents. Few studies have considered whether subsequent exposures during the pubertal transition may exacerbate impact of prenatal EDC mixtures on growth, maturation and the risk of metabolic syndrome. This center will test the overarching hypothesis that in utero and peripubertal exposures to mixtures of EDCs (bisphenol A, phthalates, lead, cadmium) will, via epigenetic mechanisms, lead to changes in gene expression and alter the tempo of physical growth and maturation as well as metabolic function and increase risk of metabolic syndrome. Because nutrients may serve as agonists or antagonists of toxic effects of environmental chemicals, we further hypothesize that dietary intake will modify the impact of EDC mixtures on metabolic outcomes.
The Specific Aims of the University of Michigan Children’s Environmental Health and Disease Protection Center (UM-CEHC) are to:
- Assess the impact of in utero and peripubertal exposures to mixtures of EDCs (bisphenol A, BPA; phthalates; lead, Pb; and cadmium, Cd) on linear growth and weight status (body mass index, BMI); sexual maturation and reproductive hormones.
- Determine whether EDC mixtures (BPA, phthalates, Pb, Cd) via epigenetic mechanisms induce oxidative stress (tyrosine oxidation products), disrupt metabolic homeostasis (free fatty acids, amino acids, Acyl-carnitine) and lead to changes in gene transcription and metabolic function.
- Conduct tissue- and age-specific unbiased epigenomic analyses (DNA methylation, chromatin structure, transcriptomics) to identify a subset of tissue-independent labile genes to serve as biomarkers of exposure-induced metabolic syndrome.
- Examine the role of dietary intake during pregnancy and adolescence in modifying the impact of EDC mixtures on metabolic homeostasis, oxidative stress and risk of metabolic syndrome.
- Foster career development by assisting new investigators in the advancement of their research skills and knowledge in translational and children's environmental health research.
- Share current research findings on the role that environmental exposures have on children's health in an accurate, relevant way that allows community members, health care professionals, and policy-makers to incorporate this new knowledge into practice for the protection of children's health.
Progress Summary:
The University of Michigan Children’s Environmental Health and Disease Prevention Center’s (UM-CEHC) three research projects are designed to provide scientific integration across shared environmental exposures and interrelated outcomes to examine the impact of EDC mixtures (BPA, phthalates, Pb, Cd) in utero and during the pubertal transition on physical growth and maturation and leading to alterations in metabolic homeostasis, oxidative stress and metabolic syndrome, using human and animal models. Projects 1 and 2 are human studies, both conducted within the Early Life Exposures in Mexico to ENvironmental Toxicants (ELEMENT) birth cohorts that have been successfully followed for over two decades. In addition to ELEMENT participants, the Michigan Mother Infant Pairs (MMIP) cohort is included in Project 2 of the UM-CEHC to extend findings from the ELEMENT cohort to a U.S. study population. Whereas Project 1 focuses on the impact of metals (Cd, Pb) and EDCs (BPA and phthalates) in utero and during peripuberty on children’s growth and sexual maturation (Overall Aim 1) in ELEMENT, Project 2 considers the effect of EDC exposures via epigenetic mechanisms to fetal and peripubertal alterations in metabolic homeostasis and oxidative stress and the potential modifying role of diet (Overall Aims 2, 3, 4) in both ELEMENT and MMIP cohorts. To parallel the human studies, Project 3 utilizes a mouse model of perinatal environmental exposures to address the influence of perinatal and peripubertal exposure mixtures and diet on life course offspring metabolic status, reproductive development and epigenetic gene regulation (Overall Aims 2, 3, 4).
During Year 4, we re-recruited ELEMENT participants plus additionael participants from the larger ELEMENT cohorts and completed all T1 visits for an expanded sample size of 550 participants. We have begun recruitment for our T2 visit and as of July 2017, have completed 186 of these visits. Progress for Project 1 in Year 4 includes exposure assessments in urine samples from the first visit for measurements of phthalates and phenols (n=280). The remainder of the urine samples from T1 for 126 adolescents (making a total sample size of n=415), as well as prenatal urine samples previously collected from mothers who did not participate in our P20 ES01817101 study (samples from approximately 165 women with at least one pregnancy urine, for a total of 415) will be sent to NSF International (Ann Arbor, MI) for EDC analysis. In the Michigan Mother Infant Pairs (MMIP) cohort, we found associations between maternal phthalate exposure early in pregnancy and at delivery in relation to gestational age and size at birth (Watkins et al, Reproductive Toxicology, 2016). In ELEMENT, preliminary findings (Watkins et al, Environ Health, 2017) show that first trimester DEHP exposure was related to higher estradiol during peripuberty, while second trimester MEP was associated with lower estradiol in males. In addition, in females, phthalates and BPA exposure across in utero development were associated with higher serum testosterone levels and higher odds of adrenarche (Watkins et al. under review). We also examined prenatal lead exposure in relation to age of menarche in girls, finding that during the second trimester only, girls whose mothers had ≥5 µg/dL prenatal blood lead reported a later age at menarche compared to girls with prenatal blood lead levels <5 µg/dL (confounder-adjusted HR= 0.59, 95% CI 0.28 to 0.90; P=0.05). (Jansen and Zhou et al, under review). In other analyses, we found that in utero phthalate and BPA exposure were associated with higher ADHD symptoms, with differences in sex and exposure timing (Watkins et al, in preparation).
Progress for Project 2 in Year 4 included completion of DNA methylation at >850,000 CpG sites in 34 girls in the ELEMENT cohort and completed targeted metabolomics and fasting insulin on 208 of the ELEMENT adolescent participants. In addition, laboratory of classic markers of metabolic risk and untargeted metabolomics are being completed on n=415 adolescent participants from the first (T1) visit. The MMIP cohort completed profiling in the epigenome in 48 cord blood leukocyte samples, completed shotgun lipidomic and untargeted metabolomics analyses in 56 mother-child dyads and expanded exposure assessment to 12 phenols, 17 metals and 12 phthalate metabolites in first trimester maternal urine samples from the 56 dyads with lipidomics and metabolomics.
ELEMENT Cohorts: During Year 4, we re-recruited ELEMENT participants from our P20 ES01817101/RD834800 (PI: Peterson) plus additional participants from the ELEMENT cohorts at two time points. We completed the first P01 visits in November 2016, expanding our sample size from 400 to 550. We began data collection for the second P01 follow up visit in December 2016, and have completed 186 visits as of July 2017, with a similar pace of re-recruitment as for the first P01 time point. We conducted two database “breaks” in Year 4, in June 2016 and January 2017, transferring data collected at the first P01 visit from Mexico to UM. We shipped all blood and serum samples from the first visit to UM to begin laboratory analyses of untargeted metabolomics and metabolic biomarkers, scheduled for April 2017. We have begun DNA isolation from these blood samples and have performed DNA methylation analysis at candidate genes in a subset of these samples that have data from birth and the peripubertal visit. In an urinary analysis and assessment of dietary intake of cadmium from 250 children and their mothers during the third trimester, we found children consumed more dietary cadmium than pregnant women and there was a positive association of fruit and vegetable intake among women and potato consumption among children with urinary cadmium (Moynihan et al, Sci Total Environ, 2016). Additionally, an analysis of prenatal and concurrent cadmium exposure during adolescence showed associations between prenatal exposure and negative effects on abdominal and peripheral adiposity in girls but not boys, emphasizing sex-dependent adiposity effects of cadmium exposure in utero that persist into adolescence (Moynihan et al., under review). In preliminary analyses of prenatal and peripubertal diet, we found antioxidant intake attenuated or reversed the cardiometabolic effects of lead measured during adolescence (Moynihan et al., in preparation). Laboratory analysis of targeted and untargeted metabolomics and lipidomic features and fasting insulin in the peripubertal sample at P20 visit (n = 250) have been completed. Among girls in this sample, we recently found third trimester mono(3-carboxypropyl) mono(2-ethyl-5-carboxypentyl) and mono(2-ethyl-5-hydroxyhexyl) (MEHHP) phthalates were associated with several known metabolites, primarily markers of lipid metabolism, that were not detected in clinical markers of cardiometabolic risk (Peterson and Goodrich, accepted for presentation, ISEE Sydney 2017). Laboratory analyses of untargeted metabolomics and clinical metabolic markers (fasting insulin, glucose, serum lipids) currently are underway on n=415 of the adolescents from T1 visit and will be complete by September/October 2017. We also completed analyzing the first visit genome-wide DNA methylation in 34 girls at birth and at the peripubertal visit. In December 2016, we applied for and received a CHEAR program project that would allow for analyzing urinary polycyclic aromatic hydrocarbons (PAHs) concentrations in ELEMENT participants during three periods, prenatal, early adolescence and late adolescence; genome-wide DNA methylation via Infinium MethylationEPIC BeadChip during late adolescence and in a subset at birth and early adolescence; and conducting serum untargeted metabolomics profiles during late adolescence in 195 ELEMENT participants.
MMIP Cohort: During Year 4, we analyzed urinary phthalates and their association with birth size and gestational age, which varies by sex and exposure timing (Watkins et al, Reproductive Toxicology, 2016). We also found that maternal lipids are associated with developmental epigenetic programming (Marchlewicz et al, Scientific Reports, 2016). We completed exposure, metabolomics and epigenomics analyses on a subset of 56 MMIP families: we analyzed phthalates, phenols and metals in the first trimester maternal urine; shotgun lipidomics and untargeted metabolomics on first trimester maternal samples, term samples and infant cord blood; and epigenome-wide DNA methylation on cord blood leukocyte samples (Montrose et al, in preparation).
Project 3 is being implemented in the viable yellow agouti (Avy) mouse model. In Years 1-4, seven cohorts of mating pairs and litters were established and followed until 10 months of age to assess whether in utero high-fat diets modify the effects of perinatal BPA exposure on metabolic, hormonal and oxidative stress parameters throughout the life course, and to identify DNA methylation alterations underlying such effects. In Year 4, we compared the metabolic effects of Western High Fat Diets (HFD) and Mediterranean HFDs and found that BPA increased 10 month liver 8-isoprostane and both HFDs increased serum leptin and liver triglyceride levels. We also ran fatty liver and insulin resistance RT2 Profiler PCR arrays on hepatic RNA on the 10 month males and females and found that the impact of BPA was negated by both HFDs. The pups exposed to the Mediterranean HFD had higher weekly weights with 5-10 months of age and greater hepatic triglycerides compared to controls but no differences were observed with BPA or Western diet. We found perinatal HFD appears to have a greater impact on life course metabolic health than perinatal BPA exposure and concurrent BPA exposure does not appear to exacerbate effects of either HFD.
In Year 4, we studied exposure to two phthalates mixtures, DEHP+DINP and DEHP+DINP+DBP, as well as these phthalates in isolation and found that coat colors of mice exposed to DBP only and DEHP+DBP+DINP shifted towards the brown hypermethylated phenotype suggesting that perinatal phthalate exposure alters DNA methylation at the Avy allele. In addition, perinatal exposures to phthalates and phthalate mixtures alter the pancreas redox environment in early life and are associated with metabolic phenotypes in adulthood, and will be presented by Ph.D. student, Ms. Kari Neier at the 2017 Gordon Research Seminar on Cellular and Molecular Mechanisms of Toxicity. In general, males exposed to DEHP had more reducing glutathione and cysteine than controls at post-natal-day 21, and also had decreased relative pancreas weights at 10 months. Thus, early alterations in pancreas redox potentials may influence metabolic phenotypes in later life. Additional evaluations of pancreas morphology and glucose homeostasis are ongoing to further characterize relationships between early life pancreatic redox environment and adverse metabolic effects.
In examining the Aim 3 epigenetic tissue specificity and drift with age, we analyzed matched mouse-tail and blood samples for epigenetic age related DNA methylation changes and results were published in Reproductive Toxicology (2016) and presented by Mr. Kochmanski at the CCT ToxicoEpigenetics Meeting in November 2016 and at Society of Toxicology in March 2017. Project 3 personnel were invited to publish a Contemporary Review in Toxicological Sciences introducing the term “Environmental Deflection,” which describes the effects of toxicant exposures on the aging epigenome (Kochmanski et al, 2017).
In Year 4, the COTC collaborated with other University of Michigan Centers, local, regional and national partners. We worked with the Michigan Lifestage Environmental Exposures and Disease (M-LEEaD) Core Center to host several external investigator seminars, including a talk by Dr. Marc Weisskopf from Harvard School of Public Health on the relationship between air pollution and autism in March 2017. In Year 4, we also continued to work closely with our Community Advisory Board (CAB) in the Grand Rapids/Kent County, MI, area, including Head Start for Kent County, Healthy Homes Coalition of West Michigan and the Kent County Health Department. We developed and piloted a survey on environmental exposures in the home environment with a group of Head Start parents and are currently incorporating feedback to generate a home environment screener to be used in this community in conjunction with an observational screener developed by Healthy Homes for home visitors to conduct with Head Start families. In Year 5, we will apply for several internal translational science grants to perform the screeners in a variety of Head Start home visits and refer several families to the services of Healthy Homes. Furthermore, we are collaborating with the UM SPH Flint Water Task Force to revise and finalize training materials for Community Health Workers on nutrition and lead mitigation. These presentations were piloted with Flint Community Health Workers in April 2017 and will be placed online for public access and use on the Michigan Public Health Training Center’s website Exit.
In addition to our work with the local community, in Year 4 we continued our focus on promoting community engagement in collaboration with our fieldwork host site, INSP in Mexico. We have worked closely with an anthropologist, Dr. Elizabeth Roberts, who is studying several of the families in the ELEMENT cohort through an NSF-funded grant. Dr. Roberts’s work has informed our continued improvement in retention strategies of ELEMENT participants as well as engagement in the Mexico City communities where these participants reside. Our fieldwork team developed a growth chart to provide participants with their weight and height trajectories since birth, as well as their blood lead levels from measurements we are using in our research studies. At the March 2017 meeting with ELEMENT and PROGRESS investigators previously mentioned, we collaborated on participant engagement topics for both cohorts and several INSP members presented results from a participant engagement questionnaire we apply at each visit.
Future Activities:
In Year 5, we plan to complete the second wave of ELEMENT data collection (T2). For Project 1, we will assess the impact of in utero and peripubertal EDC exposure on height and BMI velocity using repeated exposure and anthropometry data from the UM Formative Children’s Environmental Health Center (P20ES018171/RD83480019, PI: Peterson) and the first visit from the current study (Aim 1). We will also utilize urinary metals data from the ELEMENT mothers and children to evaluate how exposure to EDC mixtures during in utero and peripubertal development affects sexual maturation and reproductive hormone levels (Aim 2). Finally, for Aim 3, we will analyze all of the first time point exposure and hormone data to assess these levels during the pubertal transition. In addition, we will submit two additional manuscripts, one describing predictors of metals exposure in children in the ELEMENT cohort and the second describing associations between in utero phthalate and BPA exposure in relation to ADHD behaviors in childhood.
For Project 2 Aims related to the ELEMENT cohort, we will complete laboratory analysis of complete metabolomics data, including targeted and untargeted analysis. We will also collaborate with Dr. James Hébert from the University of South Carolina to examine the relationship between dietary inflammatory markers and cardiometabolic outcomes in the ELEMENT cohort using the Dietary Inflammatory Index. Further, we will be combining the Mediterranean diet from Project 3 to ELEMENT food frequency data to create a Mediterranean diet score and relate the score to various metabolic outcomes in adolescence.
For both ELEMENT (adolescent samples) and MMIP (maternal samples), we will complete genome-wide DNA methylation analyses from a subset of samples via the Infinium MethylationEPIC BeadChip. We will also quantify DNA methylation at key genes related to outcomes of interest among 400 ELEMENT children using DNA from the late adolescent visit. We will then analyze the data to relate exposures to DNA methylation profiles and ultimately to metabolomics and health outcome data. We will also complete Aim 3 proposed candidate gene DNA methylation analyses in ELEMENT (DNA from children at 3 developmental periods) and MMIP (infant and maternal DNA). In addition, funded through a University of Michigan Lifestage Environmental Exposures and Disease Center (M-LEEaD, P30 Center) pilot, we have completed measures of inflammatory markers on the maternal first trimester, delivery samples and cord blood in the MMIP cohort, which will be analyzed in Year 5.
For Project 3, in Year 5, we will continue the assessment of epigenetic tissue specificity and time-dependent epigenetic drift using genome wide whole methylome, hydroxymethylation, and transciptome analysis. We will also continue the tissue specific epigenetic, oxidative stress and metabolic parameter analysis. We will focus on publishing our results from Aims 1 and 2 during Year 5.
The COTC will continue partnerships in Kent County, Michigan, in Year 5, by continuing to evaluate and refine our parent and in-home screeners and applying for internal University of Michigan Institute for Clinical & Health Research (MICHR) Clinical and Translational Science Awards (CTSA) Program grant. We aim to work with Head Start for Kent County, Healthy Homes of West Michigan, and the Kent County Health Department to create trainings for home visitors from Head Start to conduct visual environmental screeners of homes and work with parents to understand potential health hazards. We will also investigate the association between home environment and toxicant exposures and Head Start attendance, as school attendance is linked to other educational outcomes. The Michigan Public Health Training Center from the UM SPH will help the COTC to facilitate meetings and present community-based participatory research (CBPR) concepts to the CAB to strengthen our partnerships with community members. The COTC will continue to work with the UM Flint Water Task Force to refine and disseminate the presentation on lead and nutrition to other communities, including Grand Rapids. Furthermore, our ELEMENT research team applied for cohort maintenance grant: 1R24ES028502-01, Peterson/Song; Multigenerational Effects of Toxicant Exposures on Life Course Health and Neurocognitive Outcomes in the ELEMENT Birth Cohorts (pending), which is focused on data sharing and participant engagement. Through the R24, we plan to enhance our efforts to retain participants and work closely with the fieldwork team to ensure our engagement strategies are culturally appropriate and tailored to our participants’ feedback received from the participant perception questionnaires.
References:
Watkins DJ, Sanchez BN, Tellez-Rojo MM, Lee JM, Mercado-Garcia A, Blank-Goldenberg C, Peterson KE, Meeker JD. Impact of phthalate and BPA exposure during the in utero windows of susceptibility on reproductive hormones and sexual maturation in peripubertal males. Environ Health. 2017 Jun 21;16(1):69.
Moynihan M, Peterson KE, Cantoral A, Song PXK, Jones A, Solano-Gonzalez M, Meeker JD, Basu N, Tellez-Rojo MM. Dietary predictors of urinary cadmium among pregnant women and children. Sci Total Environ. 2017 Jan;575:1255-1262.et al, 2017
Marchlewicz EH, Dolinoy DC, Tang L, Milewski S, Jones TR, Goodrich JM, Soni T, Domino SE, Song PX, Burant C, Padmanabhan V. Lipid metabolism is a key mediator of developmental epigenetic programming. Scientific Reports. 2016 Oct;6:34857.
Kochmanski J, Montrose L, Goodrich JM, Dolinoy DC. Environmental deflection: the impact of toxicant exposures on the aging epigenome. Toxicol Sci. 2017 Apr;156(2):325-335.
Journal Articles: 66 Displayed | Download in RIS Format
Other center views: | All 97 publications | 73 publications in selected types | All 66 journal articles |
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Baek J, Sancehz BN, Berrocal VJ, Sanchez-Vaznaugh EV. Distributed lag models: examining associations between the built environment and health. Epidemiology 2016;27(1):116-124. |
R835436 (2016) R835436 (2017) |
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Baek J, Sanchez-Vaznaugh EV, Sanchez BN. Hierarchial distributed-lag models: exploring varying geographic scale and magnitude in associations between built environment and health. American Journal of Epidemiology 2016;183(6):583-592. |
R835436 (2016) R835436 (2017) |
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Breton CV, Marsit CJ, Faustman E, Nadeau K, Goodrich JM, Dolinoy DC, Herbstman J, Holland N, LaSalle JM, Schmidt R, Yousefi P, Perera F, Joubert BR, Wiemels J, Taylor M, Yang IV, Chen R, Hew KM, Freeland DM, Miller R, Murphy SK. Small-magnitude effect sizes in epigenetic end points are important in children's environmental health studies:the Children's Environmental Health and Disease Prevention Research Center's Epigenetics Working Group. Environmental Health Perspectives 2017;125(4):511-526. |
R835436 (2017) R834515 (Final) R836159 (2018) |
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Buxton M, Perng W, Tellez-Rojo M, Rodriguez-Carmona Y, Cantoral A, Sanchez B, Rivera-Gonzalez L, Gronlund C, Scivappa N, Hebert J, O'Neill M, Peterson K. Particulate matter exposure, dietary inflammatory index and preterm birth in Mexico city, Mexico. ENVIRONMENTAL RESEARCH 2020;189(109852). |
R835436 (Final) |
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Cantonwine DE, Hauser R, Meeker JD. Bisphenol A and human reproductive health. Expert Review of Obstetrics & Gynecology 2013;8(4):329-335. |
R835436 (2014) R835436 (2015) R835436 (2017) |
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Cantoral A, Tellez-Rojo MM, Levy TS, Hernandez-Avila M, Schnaas L, Hu H, Peterson KE, Ettinger AS. Differential association of lead on length by zinc status in two-year old Mexican children. Environmental Health 2015;14:95 (7 pp.). |
R835436 (2015) R835436 (2017) |
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Cantoral A, Tellez-Rojo MM, Ettinger AS, Hu H, Hernandez-Avila M, Peterson K. Early introduction and cumulative consumption of sugar-sweetened beverages during the pre-school period and risk of obesity at 8-14 years of age. Pediatric Obesity 2016;11(1):68-74. |
R835436 (2014) R835436 (2015) R835436 (2016) R835436 (2017) |
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Chavarro JE, Watkins DJ, Afeiche MC, Zhang Z, Sanchez BN, Cantonwine D, Mercado-Garcia A, Blank-Goldenberg C, Meeker JD, Tellez-Rojo MM, Peterson KE. Validity of self-assessed sexual maturation against physician assessments and hormone levels. The Journal of Pediatrics 2017;186:172-178.e3. |
R835436 (2016) R835436 (2017) |
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Chen Y-H, Ferguson KK, Meeker JD, McElrath TF, Mukherjee B. Statistical methods for modeling repeated measures of maternal environmental exposure biomarkers during pregnancy in association with preterm birth. Environmental Health 2015;14(1):9 (13 pp.). |
R835436 (2014) R835436 (2015) R835436 (2017) |
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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. |
R835436 (2014) R835436 (2015) R835436 (2017) |
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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. |
R835436 (2014) R835436 (2015) R835436 (2017) |
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Ferguson KK, McElrath TF, Chen Y-H, Loch-Caruso R, Mukherjee B, Meeker JD. Repeated measures of urinary oxidative stress biomarkers during pregnancy and preterm birth. American Journal of Obstetrics & Gynecology 2015;212(2):208.e1-208.e8. |
R835436 (2014) R835436 (2015) R835436 (2017) |
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Ferguson KK, McElrath TF, Cantonwine DE, Mukherjee B, Meeker JD. Phthalate metabolites and bisphenol-A in association with circulating angiogenic biomarkers across pregnancy. Placenta 2015;36(6):699-703. |
R835436 (2015) R835436 (2017) |
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Ferguson KK, Meeker JD, Cantonwine DE, Chen Y-H, Mukherjee B, McElrath TF. Urinary phthalate metabolite and bisphenol A associations with ultrasound and delivery indices of fetal growth. Environment International 2016;94:531-537. |
R835436 (2016) R835436 (2017) R834513 (Final) R836155 (2017) R836155 (2020) R836155C003 (2017) |
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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. |
R835436 (2014) R835436 (2015) R835436 (2017) R834800 (2013) |
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Fossee E, Zamora A, Peterson K, Cantoral A, Perng W, Tellez-Rojo M, Torres-Olascoaga L, Jansen E. Prenatal dietary patterns in relation to adolescent offspring adiposity and adipokines in a Mexico City cohort. JOURNAL OF DEVELOPMENTAL ORIGINA OF HEALTH AND DISEASE 2023;PII S2040174422000678:1-10 |
R835436 (Final) |
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Goodman C, Bashash M, Green R, Song P, Peterson K, Schnass L, Mercado-Garcia A, Martinez-Medina S, Hernandez-Avila M, Martiniz-Mier A, Tellez-Rojo M, Hu H, Till C. Domain-specific effects of prenatal fluoride exposure on child IQ at 4, 5, and 6-12 years in the ELEMENT cohort. ENVIRONMENTAL RESEARCH 2022;211:112993. |
R835436 (Final) |
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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. |
R835436 (2014) R835436 (2015) R835436 (2017) |
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Goodrich JM, Dolinoy DC, Sanchez BN, Zhang Z, Meeker JD, Mercado-Garcia A, Solano-Gonzalez M, Hu H, Tellez-Rojo MM, Peterson KE. Adolescent epigenetic profiles and environmental exposures from early life through peri-adolescence. Environmental Epigenetics 2016;2(3):dvw018 (11 pp.). |
R835436 (2016) R835436 (2017) |
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Goodrich JM, Chou HN, Gruninger SE, Fraznblau A, Baus N. Exposures of dental professionals to elemental mercury and methylmercury. Journal of Exposure Science and Environmental Epidemiology 2016;26(1):78-85. |
R835436 (2016) R835436 (2017) |
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Huang S, Hu H, Sanchez BN, Peterson KE, Ettinger AS, Lamadrid-Figueroa H, Schnaas L, Mercado-Garcia A, Wright RO, Basu N, Cantonwine DE, Hernandez-Avila M, Tellez-Rojo MM. Childhood blood lead levels and symptoms of attention deficit hyperactivity disorder (ADHD):a cross-sectional study of Mexican children. Environmental Health Perspectives 2016;124(6):868-874. |
R835436 (2016) R835436 (2017) |
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Jansen EC, Zhou L, Song PXK, Sanchez BN, Mercado A, Hu H, Solano M, Peterson KE, Tellez-Rojo MM. Prenatal lead exposure in relation to age at menarche: results from a longitudinal study in Mexico City. Journal of Developmental Origins of Health and Disease 2018;9(4):467-472. |
R835436 (2017) |
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Jansen EC, Zhou L, Perng W, Song PXK, Tellez-Rojo MM, Mercado A, Peterson KE, Cantoral A. Vegetables and lean proteins-based and processed meats and refined grains-based dietary patterns in early childhood are associated with pubertal timing in a sex-specific manner: a prospective study of children from Mexico City. Nutrition Research 2018;56:41-50. |
R835436 (2017) |
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Jansen E, Burgess H, Chervin R, Dolinoy D, Tellez-Rojo M, Cantoral A, Olasocoaga-Torres L, Lee J, Dunietz G, O'Brien L, Peterson K. Sleep duration and timing are prospectively linked with insulin resistance during late adolescence. OBESITY 2023;31(4):912-922. |
R835436 (Final) |
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Kasper N, Peterson KE, Zhang Z, Ferguson KK, Sanchez BN, Cantoral A, Meeker JD, Tellez-Rojo MM, Pawlowski CM, Ettinger AS. Association of bisphenol A exposure with breastfeeding and perceived insufficient milk supply in Mexican women. Maternal and Child Health Journal 2016;20(8):1713-1719. |
R835436 (2015) R835436 (2016) R835436 (2017) |
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Kochmanski JJ, Marchlewicz EH, Cavalcante RG, Perera BPU, Sartor MA, Dolinoy DC. Longitudinal effects of developmental bisphenol A exposure on epigenome-wide DNA hydroxymethylation at imprinted loci in mouse blood. Environmental Health Perspectives 2018;126(7):077006 (16 pp.). |
R835436 (2017) |
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Kochmanski J, Montrose L, Goodrich JM, Dolinoy DC. Environmental deflection: the impact of toxicant exposures on the aging epigenome. Toxicological Sciences 2017;156(2):325-335. |
R835436 (2016) R835436 (2017) |
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Kochmanski J, Marchlewicz EH, Savidge M, Montrose L, Faulk C, Dolinoy DC. Longitudinal effects of perinatal bisphenol A and variable diet exposures on epigenetic drift in mice. Reproductive Toxicology 2017;68:154-163. |
R835436 (2016) R835436 (2017) |
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Kochmanski J, Marchlewicz EH, Dolinoy DC. Longitudinal effects of developmental bisphenol A, variable diet, and physical activity on age-related methylation in blood. Environmental Epigenetics 2018;4(3):dvy017 (10 pp.). |
R835436 (2017) |
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Lewis RC, Meeker JD. Biomarkers of exposure to molybdenum and other metals in relation to testosterone among men from the United States National Health and Nutrition Examination Survey 2011-2012. Fertility and Sterility 2015;103(1):172-178. |
R835436 (2014) R835436 (2015) R835436 (2017) |
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Lewis RC, Johns LE, Meeker JD. Serum biomarkers of exposure to perfluoroalkyl substances in relation to serum testosterone and measures of thyroid function among adults and adolescents from NHANES 2011-2012. International Journal of Environmental Research and Public Health 2015;12(6):6098-6114. |
R835436 (2014) R835436 (2015) R835436 (2017) R836155 (2020) R836155C003 (2017) |
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Lewis RC, Johns LE, Meeker JD. Exploratory analysis of the potential relationship between urinary molybdenum and bone mineral density among adult men and women from NHANES 2007-2010. Chemosphere 2016;164:677-682. |
R835436 (2016) R835436 (2017) |
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Liu Y, Peterson KE. Maternal exposure to synthetic chemicals and obesity in the offspring: recent findings. Current Environmental Health Reports 2015;2(4):339-347. |
R835436 (2015) R835436 (2017) |
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Marchlewicz EH, Dolinoy DC, Tang L, Milewski S, Jones TR, Goodrich JM, Soni T, Domino SE, Song PXK, Burant C, Padmanabhan V. Lipid metabolism is associated with developmental epigenetic programming. Scientific Reports 2016;6:34857 (13 pp.). |
R835436 (2016) R835436 (2017) |
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Meeker JD, Ferguson KK. Urinary phthalate metabolites are associated with decreased serum testosterone in men, women, and children from NHANES 2011-2012. The Journal of Clinical Endocrinology and Metabolism 2014;99(11):4346-4352. |
R835436 (2014) R835436 (2015) R835436 (2017) |
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Montrose L, Padmanabhan V, Goodrich JM, Domino SE, Treadwell MC, Meeker JD, Watkins DJ, Dolinoy DC. Maternal levels of endocrine disrupting chemicals in the first trimester of pregnancy are associated with infant cord blood DNA methylation. Epigenetics 2018;13(3):301-309. |
R835436 (2017) |
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Moynihan M, Peterson KE, Cantoral A, Song PXK, Jones A, Solano-Gonzalez M, Meeker JD, Basu N, Tellez-Rojo MM. Dietary predictors of urinary cadmium among pregnant women and children. Science of the Total Environment 2017;575:1255-1262. |
R835436 (2016) R835436 (2017) |
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Neier K, Marchlewicz EH, Dolinoy DC, Padmanabhan V. Assessing human health risk to endocrine disrupting chemicals: a focus on prenatal exposures and oxidative stress. Endocrine Disruptors (Austin);2015;3(1):e1069916 (8 pp.). |
R835436 (2015) R835436 (2017) |
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Omoike OE, Lewis RC, Meeker JD. Association between urinary biomarkers of exposure to organophosphate insecticides and serum reproductive hormones in men from NHANES 1999-2002. Reproductive Toxicology 2015;53:99-104. |
R835436 (2015) R835436 (2017) |
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Peretz J, Vrooman L, Ricke WA, Hunt PA, Ehrlich S, Hauser R, Padmanabhan V, Taylor HS, Swan SH, VandeVoort CA, Flaws JA. Bisphenol A and reproductive health: update of experimental and human evidence, 2007-2013. Environmental Health Perspectives 2014;122(8):775-786. |
R835436 (2014) R835436 (2015) R835436 (2017) R834593C001 (Final) R835434 (2013) R835434 (2014) |
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Perng W, Watkins DJ, Cantoral A, Mercado-Garcia A, Meeker JD, Tellez-Rojo MM, Peterson KE. Exposure to phthalates is associated with lipid profile in peripubertal Mexican youth. Environmental Research 2017;154:311-317. |
R835436 (2016) R835436 (2017) |
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Perng W, Fernandez C, Peterson KE, Zhang Z, Cantoral A, Sanchez BN, Solano-Gonzalez M, Tellez-Rojo MM, Baylin A. Dietary patterns exhibit sex-specific associations with adiposity and metabolic risk in a cross-sectional study in urban Mexican adolescents. The Journal of Nutrition 2017;147(10):1977-1985. |
R835436 (2017) |
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Perng W, Hector EC, Song PXK, Tellez Rojo MM, Raskind S, Kachman M, Cantoral A, Burant CF, Peterson KE. Metabolomic determinants of metabolic risk in Mexican adolescents. Obesity (Silver Spring) 2017;25(9):1594-1602. |
R835436 (2017) |
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Sanchez-Vaznaugh EV, Sanchez BN, Crawford PB, Egerter S. Association between competitive food and beverage policies in elementary schools and childhood overweight/obesity trends: differences by neighborhood socioeconomic resources. JAMA Pediatrics 2015;169(5):e150781 (17 pp.). |
R835436 (2014) R835436 (2015) R835436 (2017) |
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Silver MK, Lozoff B, Meeker JD. Blood cadmium is elevated in iron deficient U.S. children: a cross-sectional study. Environmental Health 2013;12(1):117 (9 pp.). |
R835436 (2014) R835436 (2015) R835436 (2017) |
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Somers EC, Monrad SU, Warren JS, Solano M, Schnaas L, Hernandez-Avila M, Tellez-Rojo MM, Hu H. Antinuclear antibody prevalence in a general pediatric cohort from Mexico City: discordance between immunofluorescence and multiplex assays. Clinical Epidemiology 2017;9:1-8. |
R835436 (2016) R835436 (2017) |
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Sun Z, Tao Y, Li S, Ferguson KK, Meeker JD, Park SK, Batterman SA, Mukherjee B. Statistical strategies for constructing health risk models with multiple pollutants and their interactions: possible choices and comparisons. Environmental Health 2013;12(1):85 (19 pp.). |
R835436 (2014) R835436 (2015) R835436 (2017) |
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Tao Y, Sanchez BN, Mukherjee B. Latent variable models for gene-environment interactions in longitudinal studies with multiple correlated exposures. Statistics in Medicine 2015;34(7):1227-1241. |
R835436 (2014) R835436 (2015) R835436 (2017) |
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Trentacosta CJ, Davis-Kean P, Mitchell C, Hyde L, Dolinoy D. Environmental contaminants and child development. Child Developmental Perspectives 2016;10(4):228-233. |
R835436 (2016) R835436 (2017) |
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Vandenberg LN, Gerona RR, Kannan K, Taylor JA, van Breemen RB, Dickenson CA, Liao C, Yuan Y, Newbold RR, Padmanabhan V, vom Saal FS, Woodruff TJ. A round robin approach to the analysis of bisphenol A (BPA) in human blood samples. Environmental Health 2014;13(1):25 (20 pp.). |
R835436 (2014) R835436 (2015) R835436 (2017) R834678C001 (Final) |
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Veiga-Lopez A, Pennathur S, Kannan K, Patisaul HB, Dolinoy DC, Zeng L, Padmanabhan V. Impact of gestational bisphenol A on oxidative stress and free fatty acids: human association and interspecies animal testing studies. Endocrinology 2015;156(3):911-922. |
R835436 (2014) R835436 (2015) R835436 (2017) |
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Veiga-Lopez A, Kannan K, Liao C, Ye W, Domino S, Padmanabhan V. Gender-specific effects on gestational length and birth weight by early pregnancy BPA exposure. Journal of Clinical Endocrinology and Metabolism 2015;100(11):E1394-E1403. |
R835436 (2015) R835436 (2017) |
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Watkins DJ, Tellez-Rojo MM, Ferguson KK, Lee JM, Solano-Gonzalez M, Blank-Goldenberg C, Peterson KE, Meeker JD. In utero and peripubertal exposure to phthalates and BPA in relation to female sexual maturation. Environmental Research 2014;134:233-241. |
R835436 (2014) R835436 (2015) R835436 (2017) |
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Watkins DJ, Peterson KE, Ferguson KK, Mercado-Garcia A, Tamayo y Ortiz M, Cantoral A, Meeker JD, Tellez-Rojo MM. Relating phthalate and BPA exposure to metabolism in peripubescence: the role of exposure timing, sex, and puberty. Journal of Clinical Endocrinology & Metabolism 2016;101(1):79-88. |
R835436 (2015) R835436 (2016) R835436 (2017) |
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Watkins DJ, Fortenberry GZ, Sanchez BN, Barr DB, Panuwet P, Schnaas L, Osorio-Valencia E, Solano-Gonzalez M, Ettinger AS, Hernandez-Avila M, Hu H, Tellez-Rojo MM, Meeker JD. Urinary 3-phenoxybenzoic acid (3-PBA) levels among pregnant women in Mexico City: distribution and relationships with child neurodevelopment. Environmental Research 2016;147:307-313. |
R835436 (2015) R835436 (2016) R835436 (2017) R836155 (2017) R836155 (2020) R836155C003 (2017) |
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Watkins DJ, Milewski S, Domino SE, Meeker JD, Padmanabhan V. Maternal phthalate exposure during early pregnancy and at delivery in relation to gestational age and size at birth: a preliminary analysis. Reproductive Toxicology 2016;65:59-66. |
R835436 (2016) R835436 (2017) R834513 (Final) |
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Watkins DJ, Sanchez BN, Tellez-Rojo MM, Lee JM, Mercado-Garcia A, Blank-Goldenberg C, Peterson KE, Meeker JD. Impact of phthalate and BPA exposure during the in utero windows of susceptibility on reproductive hormones and sexual maturation in peripubertal males. Environmental Health 2017;16(1):69 (10 pp.). |
R835436 (2016) R835436 (2017) R835436 (Final) |
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Watkins DJ, Sanchez BN, Tellez-Rojo MM, Lee JM, Mercado-Garcia A, Blank-Goldenberg C, Peterson KE, Meeker JD. Phthalate and bisphenol A exposure during in utero windows of susceptibility in relation to reproductive hormones and pubertal development in girls. Environmental Research 2017;159:143-151. |
R835436 (2017) |
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Wu J, Wen XW, Faulk C, Boehnke K, Zhang H, Dolinoy DC, Xi C. Perinatal lead exposure alters gut microbiota composition and results in sex-specific body weight increases in adult mice. Toxicological Sciences 2016;151(2):324-333. |
R835436 (2016) R835436 (2017) |
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Yang TC, Peterson KE, Meeker JD, Sanchez BN, Zhang Z, Cantoral A, Solano M, Tellez-Rojo MM. Bisphenol A and phthalates in utero and in childhood: association with child BMI z-score and adiposity. Environmental Research 2017;156:326-333. |
R835436 (2016) R835436 (2017) |
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Yang TC, Peterson KE, Meeker JD, Sanchez BN, Zhang Z, Cantoral A, Solano M, Tellez-Rojo MM. Exposure to bisphenol A and phthalates metabolites in the third trimester and BMI trajectories. Pediatric Obesity 2018;13(9):550-557. |
R835436 (2017) |
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Zamora A, Peterson K, Goodrichy J, Tellez-Roho M, Song P, Meeker J, Dolinoy D, Torres-Olascoaga L, Cantoral A, Jansen E. Associations between exposure to phthalates, phenols, and parabens with objective and subjective measures of sleep health among Mexican women in midlife: a cross-sectional and retrospective analysis. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH 2023;Epub |
R835436 (Final) |
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Zamora A, Jansen E, Goodrich J, Tellez-Rojo M, Song P, Meeker J, Dolinoy D, Torres O, Cantoral A, Peterson K. Cross-sectional associations between phthalates, phenols, and parabens with metabolic syndrome risk during early-to-mid adolescence among a cohort of Mexican youth. ENVIRONMENTAL SCIENCE 2023;116706 |
R835436 (Final) |
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Zhang K, Buxton M, Rodriguez-Carmona Y, Peterson K, Liu Y, Burgess H, Cantoral A, Tellez-Rojo M, Torres-Olasconaga L, Arboleda-Merino L, Jansen E. Duration, timing, and consistency of sleep in relation to inflammatory cytokines in Mexican adolescents. SLEEP MEDICINE 2022;100:103-111. |
R835436 (Final) |
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Zhang Z, O’Neill MS, Sanchez BN. Using a latent variable model with non-constant factor loadings to examing PM2.5 constituents related to secondary inorganic aerosols. Statistical Modeling 2016;16(2):91-113. |
R835436 (2016) R835436 (2017) |
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Zhou Y, Wang P, Wang X, Zhu J, Song PX. Sparse multivariate factor analysis regression models and its applications to integrative genomics analysis. Genetic Epidemiology 2017;41(1):70-80. |
R835436 (2016) R835436 (2017) |
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Supplemental Keywords:
Endocrine disrupting chemicals, EDCs, epigenetics, maturation, metabolic syndromeProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
- Final Report
- 2017 Progress Report
- 2015 Progress Report
- 2014 Progress Report
- 2013 Progress Report
- Original Abstract
66 journal articles for this center