Grantee Research Project Results

2012 Progress Report: Children's Environmental Health and Disease Prevention Research Centers: Formative Centers

EPA Grant Number: R834678
Center: Center for Integrative Research on Childhood Leukemia and the Environment - 2015
Center Director: Metayer, Catherine
Title: Children's Environmental Health and Disease Prevention Research Centers: Formative Centers
Investigators: Woodruff, Tracey J. , Steinauer, Jody , McMaster, Michael , Stotland, Naomi , Sutton, Patrice
Current Investigators: Woodruff, Tracey J. , Fisher, Susan J. , McMaster, Michael , Stotland, Naomi , Sutton, Patrice , Gerona, Roy
Institution: University of California - San Francisco
EPA Project Officer: Hahn, Intaek
Project Period: May 5, 2010 through May 4, 2014
Project Period Covered by this Report: May 5, 2012 through May 4,2013
Project Amount: $762,983
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:

R834678C001: Assessing Maternal and Fetal Exposures to Chemicals During the Second Trimester

The objectives of this research remain the same—to generate unprecedented data on chemical exposures during the second trimester of pregnancy, when certain aspects of fetal development are particularly vulnerable to disruption. The specific aims of the project are to (1) compare maternal and fetal exposures to BPA during the second trimester, and (2) explore the feasibility and accuracy of using maternal biological biomonitoring results to predict fetal exposures.

R834678C002: Assessing the Effects of BPA Exposure on Early Human Development

The goal of this work is to investigate how BPA exposure alters gene expression in human embryonic stem cells (hESCs), and to begin to understand the functional consequences of the changes we observe on early development. Aim 1 included establishment and optimization of in vitro models for exposure and microarray analysis of changes in gene expression that resulted from BPA treatment at doses that have been measured in human studies. Aim 2 experiments were designed to validate the candidate targets and pathways we identified by differentiating BPA-treated hESCs and studying their composition with regard to the progeny of the three definitive germ layers. The specific aims of the project have not been modified.

R834678C003: Predictors of Maternal Exposure to BPA During the Second Trimester of Pregnancy

The objectives of this research remain the same—to understand potential sources of exposure to BPA, and to collect data on the biological half-life of BPA. The specific aims of the project are to (1) investigate the determinants of maternal exposures to BPA during the second trimester of pregnancy, and (2) characterize the change in BPA levels in pregnant women associated with fasting.

Community Outreach and Translation Core (COTC)

(1) Communicate the meaning of the PEEC Formative Center’s research broadly; (2) Create and disseminate a science-based foundation for clinical care and policy change endorsed by key leaders; (3) Sustain and expand a collaborative network of partners; and (4) Advance public policy in the field of reproductive environmental health.

Progress Summary:

R834678C001: Assessing Maternal and Fetal Exposures to Chemicals During the Second Trimester

We have completed study recruitment. In total, we recruited 170 women from September 2010 to April 2012 (our target was 100). Women eligible for the study attended the clinic over 2 days, and we collected 125 urines from women for the first day of their visit and 111 urines from women the 2nd day of the visit, which is the day of their medical procedure. From the medical procedure, we collected 82 umbilical cord bloods, 162 placentas and 153 fetal livers.

Our collaborator in the Department of Laboratory Medicine at San Francisco General Hospital, Dr. Roy Gerona, has developed an improved method for analyzing unconjugated BPA, BPA sulfate and BPA glucuronide. To date, Dr. Gerona has measured unconjugated BPA, BPA sulfate and BPA glucuronide in all of our umbilical cord serum and urine samples and has completed the method development and preliminary analysis for a subset of the liver tissues we have collected (n = 10). Additionally, during the method development phase, Dr. Gerona discovered a source of BPA contamination in our maternal serum samples. He determined the contamination source to be from the BD Vacutainer Push Button Blood Collection Set used in the hospital. We identified a BPA-free needle (BD Vacutainer Eclipse 21G needle) and started using it on November 29, 2011. However, given the difficulty of using a straight needle versus a butterfly for the phlebotomists in the clinic, we were only able to collect 20 percent of our serum samples this way. We then tested eight different models of butterfly vacutainers and have found two BPA-free replacements for the clinic, which we have started to implement.

Results:

Among our study participants, 100 percent had detectable BPA levels in nonfasting urine. The table presents the geometric means (GM) for total BPA, BPA glucuronide, BPA sulfate and unconjugated BPA. These levels are up to 3 times higher compared to other studies measuring BPA in pregnant women in the United States and other countries worldwide, possibly due to underlying demographic and behavioral characteristics of our unique study population (lower income, 40% smokers, racially diverse population). Although unlikely, BPA analytic methods may also contribute to higher BPA levels measured, as we use an LC-MS/MS technique allows direct measurement of unconjugated BPA and BPA conjugates without enzyme hydrolysis used in previous studies, which induces sample loss. From preliminary data, maternal urinary conjugated BPA (BPA glucuronide and BPA sulfate) levels were positively associated with educational attainment, non-African American ethnicity, household income, occupational and nonoccupational exposure to paper receipts, and use of food processors, and negatively associated with wine consumption. Unconjugated BPA was positively associated with recentness of canned food consumption and negatively associated with maternal BMI. Our initial analysis indicates that receipt-related BPA exposure is a strong predictor of maternal urinary BPA, and can come from both occupational and nonoccupational receipt exposures. Further analysis is warranted, but if confirmed, it would provide scientific evidence for an important, yet often neglected, route of exposure. Another notable finding is that participants who have knowledge of BPA do not have lower urinary BPA levels, despite 40 percent of participants stating that they know about BPA and 27 percent of participants stating that they avoid BPA.

Unadjusted Concentrations	Percent > LOD	GM ng/mL (gSD)	50th percentile (ng/mL)	95th percentile (ng/mL)	Range (ng/mL)
BPA Glucuronide	99%	8.45 (1.93)	6.74	359.41	< LOD—683.42
BPA Sulfate	75%	0.77 (2.71)	0.50	109.24	< LOD—271.16
Free BPA	87%	0.26 (1.20)	0.29	1.51	< LOD—4.41
Total BPA	—	12.24 (1.77)	7.51	423.57	0.64 –– 889.67
Creatinine Unadjusted Concentrations
BPA Glucuronide	99%	6.77 (1.90)	4.67	249.76	0.03 –– 2019.33
BPA Sulfate	75%	0.62 (2.73)	0.42	80.35	0.01 –– 279.77
Free BPA	87%	0.21 (1.39)	0.25	1.61	0.01 –– 16.96
Total BPA	—	9.80 (1.79)	6.09	301.46	0.63 –– 2299.55

For the first time, we provide preliminary measurements of unconjugated and conjugated BPA in umbilical cord serum. We find the geometric mean for BPA glucuronide is 0.11 ng/mL and 0.18 ng/mL for BPA sulfate. Unconjugated BPA was detected in 47 percent of umbilical cord serum samples, and 29 percent of samples had more unconjugated BPA than conjugated. Although unconjugated BPA was not universally detected, maximum concentrations of unconjugated BPA measured in our study (52.3 ng/mL) are the highest reported to date. In a subset of samples with matched umbilical cord serum and maternal urine samples (n = 29), we found higher levels of total BPA in umbilical cord serum in approximately 20 percent of samples, and higher levels of unconjugated BPA in umbilical cord serum in 45 percent of samples. Positive correlations in unconjugated and conjugated BPA levels were also observed between the two biospecimens. No other study has provided data on fetal cord blood levels during 2nd trimester, and we have shown the importance of the sulfation metabolic pathway as an alternative to glucornidation. In our analysis of the first 10 fetal liver samples, we have found that the major form of BPA is free or unconjugated BPA, which is present in 100 percent of the samples. In addition, we have found that BPA sulfate is slightly higher in these samples than BPA glucuronide and are the first to report the two conjugates differentiated.

R834678C002: Assessing the Effects of BPA Exposure on Early Human Development

With regard to previous reporting periods, initial experiments showed that BPA treatment of a federally approved hESC cell line (UCSF4) resulted in modulation of nuclear receptors, transcription factors and their target genes as well as markers of differentiation. For example, the brachyury gene, encoding a factor important for establishment of the mesodermal lineage during gastrulation in early human embryos (Bernardo et al., 2011), was upregulated by BPA treatment. We then focused our analyses on the effects of BPA on expression of families of transcriptional regulators known to play key roles in hESC self-renewal and differentiation. Hox family members (e.g., HOX-C6, -C9, -B13, -C12, -C10 and DLX2) involved in early morphogenesis were particularly sensitive to regulation by BPA. These and other data support the hypothesis that BPA tips the balance from proliferation in an undifferentiated state toward differentiation of particular lineages in early embryos. This conclusion is also bolstered by experiments showing that BPA treatment inhibits proliferation and increases differentiation as assessed by morphological changes we observed in hESC colonies.

During the most recent funding period, we made progress on both Aims. Specifically, we performed a microarray-based global transcriptional profiling experiment in which hESCs were exposed to BPA in 2 doses (10 and 50 nM) or to estrogen or vehicle/ethanol controls. The unexpected and very interesting result was that BPA had a global effect on mRNA splicing rather than frank changes in the levels of expression of individual genes. The microarray data analysis strategy to determine exon-level changes is not included in the established methodologies and required significant methods development in our group. The current generation of Affymetrix microarrays, whole gene arrays, use random primers to initiate cDNA formation, thus capturing the entire length of transcripts from the 5’ to the 3’ end. To complement this approach, the probes on the arrays are designed to cover the entire length of each transcript. Thus, a single chip provides approximately 200,000 probes for 100,000 exons to 20,000 annotated genes and allows interrogation of quantitative differences in specific mRNA transcripts, including splice variants, at the exon level. We adapted a method using whole gene arrays (Ha et al., 2009) and open-source analytical tools within R/Bioconductor (Okoniewski et al., 2008), which allowed us to interrogate the microarray data set for the presence and extent of alternative splicing across the genome that resulted from BPA treatment. By applying this methodology, we showed that a number of genes with diverse functions in hESCs were alternatively spliced in response to BPA treatment. Quantitation of these changes in exon abundance, in terms of fold-change, is shown in Figure 1. Two patterns were observed. In the first, BPA and estrogen had similar effects, suggesting common pathways. In the second, BPA had effects that were not observed in the estrogen-treated samples. These results suggest that in the hESC system, BPA had estrogenic and nonestrogenic effects.

Interestingly, TIE1 transcripts encoding an angiopoietin receptor expressed by endothelial cells and hematopoietic precursors was alternatively spliced in response to both doses of BPA (but not estrogen). TIE1 regulates cell-adhesion molecules (VCAM-1, E-selectin and ICAM-1) and plays a key role in angiogenesis and blood vessel stability. Its role in early development is poorly understood, but alternatively spliced transcript variants encoding multiple isoforms with biological activity in vascular and inflammatory pathways have been described (Jin et al., 2008).

Another gene whose splicing was affected by BPA is SPG7, encoding paraplegin, part of the m-AAA protease complex responsible for ribosome assembly. Best known for mutations that cause spastic paraplegia type 7, altered splicing of this transcript has the potential to globally interfere with mRNA processing and translation, thereby affecting diverse cellular processes, including membrane trafficking, organelle biogenesis, protein folding and proteolysis. A splice variant of SPG7 was recently described in mice that is implicated in neurodegenerative processes (Mancuso et al., 2012). Other pathways that our data suggest may be impacted in BPA-induced splicing variation included growth factor signalling, cell motility and mitosis.

Alternative splicing is a central process for modulation of gene expression, affecting over 90 percent of human genes and greatly increasing the number of distinct protein products encoded in the genome. Constitutive and alternative splicing pathways are well-characterized, involve hundreds of genes, and are known to be affected by various drugs and xenobiotics (recently reviewed in Zaharieva et al., 2011). Our data showing BPA-induced disruption of pre-mRNA splicing in hESCs suggests that gestational exposure to this ubiquitous environmental chemical may interfere with early development by mechanisms that involve changes in protein isoform expression.

R834678C003: Predictors of Maternal Exposure to BPA During the Second Trimester of Pregnancy

In total, we collected questionnaire data from 170 study participants (our target was 100). Previously, we identified that the length of the questionnaire was interfering with study recruitment and reduced the number of questions based on preliminary responses to the questionnaire. In addition to the questionnaire data, we have also collected 80 matched pairs of fasting and nonfasting maternal urine (from both days of the medical procedure).

We have completed data entry and data validation in accordance with our Quality Management Plan. We have also completed the data analysis phase of this project producing descriptive statistics on the questionnaire as well as participant demographics collected from clinical chart abstraction records. From the charts, we collected information from the counseling records, the pregnancy evaluation, the peri-operative record, and the clinic ultrasound.

Results:

Our final study population includes 112 participants who completed the questionnaire and provided a urine sample sufficient for BPA and creatinine analysis. The questionnaire data reflects the socioeconomic status of our study population: 65 percent percent of participants had 12th grade or lower education, 81 percent used public health insurance, and 54 percent received food stamp assistance. We have also found that our study population consumes high quantities of fast foods and other paper-packaged takeout food, with a mean of 6 times/week. See the above table for our unadjusted geometric means (GM) for total BPA, BPA glucuronide, BPA sulfate and unconjugated BPA. Total BPA concentration measured in our study population are up to 3 times higher compared to other studies measuring BPA in pregnant women in the United States and other countries worldwide. Maternal urinary conjugated BPA (BPA glucuronide and BPA sulfate) levels were positively associated with educational attainment, non-African American ethnicity, household income, occupational and nonoccupational exposure to paper receipts, and use of food processors, and negatively associated with wine consumption. Unconjugated BPA was negatively associated with maternal BMI, and positively associated with recentness of canned food consumption. What is notable is that participants who have knowledge of BPA do not have lower urinary BPA levels, despite 40 percent of participants knowing about BPA and 27 percent of participants avoiding BPA.

COTC

New Faculty

Robert Gould, M.D., joined our Center in June 2012. Dr. Gould is an Associate Adjunct Professor in the Department of Obstetrics, Gynecology, and Reproductive Sciences at University of California, San Francisco (UCSF) and is the Director of Health Professional Outreach at PRHE.

Health Professional Outreach and Education

• Provided extensive technical and scientific support to the American Congress of Obstetricians and Gynecologists (ACOG) on the issue of reproductive environmental health and, in collaboration with ACOG, we surveyed the attitudes, beliefs and practices of U.S. obstetricians and gynecologists to inform our efforts to advance the science among reproductive health professionals.
• Nominated Jeanne Conry, M.D., Ph.D., incoming President of ACOG, for the EPA's Environmental Health Champion award, and EPA Administrator presented the award to Dr. Conry at a ceremony at UCSF on January 8, 2012.
• Participated in organizing and attended a September 6–7, 2012, meeting of clinicians and scientists to explore issues related to prenatal environmental exposures and health outcomes. The meeting launched an ongoing partnership to address environmental health during the prenatal and preconception period, known as the Reproductive and Children’s Environmental Health Working Group.
• Dr. Woodruff presented a lecture to UCSF medical students on reproductive environmental health, which was, to our knowledge, the first time the topic was a requirement for medical students; Dr. Gould organized medical students at UCSF around the topic at Student Organizing Fair Day at UCSF and through follow-up meetings to advance students' ideas for lectures about environmental health as an elective in their curriculum.
• Dr. Gould served on the Preconception Health Care Council, including attending quarterly meetings in Sacramento, CA.
• Held quarterly meetings of our From Advancing Science to Ensuring Prevention Alliance (FASTEP) and collaborated throughout the year with our FASTEP partners on related activities.
• Dr. Gould served on the UCSF Academic Senate Sustainability Task Force, which has the aim of implementing universitywide practices beneficial to environmental and public health.
• Dr. Gould served as a delegate to the California Medical Association (CMA) and on the Santa Clara County Medical Association's Environmental Health Committee. In 2012, CMA adopted six policies related to improved environmental health.
• Dr. Gould participated in a Reproductive Health Training at Commonweal November 13–15, 2012.

Navigating the Science

We completed the first case study demonstrating proof of concept of the Navigation Guide, a systematic and transparent method to synthesize environmental health research to make it actionable by decision-makers in clinical and policy spheres; conducted extensive outreach and education on the method and expanded our network of over 60 clinical and environmental health collaborators on the Navigation Guide Work Group; and held three Work Group webinars to gather input on the methods development and disseminate our findings.

Disseminated the Science

We disseminated 21,924 hard copy and 60,435 PDF copies of our All that Matters brochures to health professionals, their patients and the public; made over 14 presentations to our target audiences; published 7 articles directed to health professionals; had our research featured in news articles in Scientific American, Environmental Health News, and the San Francisco Chronicle, and referred to in an article in the New York Times; and participated in a January 17, 2013, Informational Briefing on How the Environment Affects Children's Health—Reports From Children's Environmental Health Research Leaders, held in California State Capitol Building.

Future Activities:

R834678C001: Assessing Maternal and Fetal Exposures to Chemicals During the Second Trimester

The data from the remaining liver samples as well as method development for placenta and amniotic fluid will take place in the coming months. Because of the costs associated with identifying the source of BPA contamination, we have decided to measure 85 placentas and 85 fetal livers, matched with our umbilical cord blood samples. We plan on publishing the results of the method development, as well as data derived from the placenta and liver tissues. Finally, we plan to present this data at the annual meeting of the International Society for Environmental Epidemiology in Basel, Switzerland, in August 2013.

R834678C002: Assessing the Effects of BPA Exposure on Early Human Development

We are continuing our work to understand the effects of the alternatively spliced mRNAs that are produced in response to BPA treatment, their protein products, and the functional consequences with regard to hESC proliferation and differentiation. We have applied for a no-cost extension to extend the project period in order to complete these experiments.

R834678C003: Predictors of Maternal Exposure to BPA During the Second Trimester of Pregnancy

The questionnaire data, along with the BPA levels in maternal urine, are currently being written up as a peer-reviewed publication entitled "Dietary, Non-Dietary, and Sociodemographic Predictors of Serum Bisphenol A Body Burden in Pregnant Women." This will be submitted to Environmental Science & Technology in the spring of 2013. Also, a paper examining the levels in fasting versus nonfasting maternal urine will be completed in the summer of 2013. Finally, we plan to present this data at the annual meeting of the International Society for Environmental Epidemiology in Basel, Switzerland in August 2013.

COTC

This was the third and final year of the grant. Our papers on the Navigation Guide case study and the ACOG survey are in preparation and will be submitted for publication by the end of May.

References:

Bernardo AS, Faial T, Gardner L, Niakan KK, Ortmann D, Senner CE, Callery EM, Trotter MW, Hemberger M, Smith JC, Bardwell L, Moffett A, Pedersen RA. BRACHYURY and CDX2 mediate BMP-induced differentiation of human and mouse pluripotent stem cells into embryonic and extraembryonic lineages. Cell Stem Cell 2011;(2):144-55.

Ha KCh, Coulombe-Huntington J, Majewski J. Comparison of Affymetrix Gene Array with the Exon Array shows potential application for detection of transcript isoform variation. BMC Genomics 2009;10:519.

Jin P, Zhang J, Sumariwalla PF, Ni I, Jorgensen B, Crawford D, Phillips S, Feldmann M, Shepard HM, Paleolog EM Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis. Arthritis Res Ther 2008;10(4).

Mancuso G, Barth E, Crivello P, Rugarli EI. Alternative splicing of Spg7, a gene involved in hereditary spastic paraplegia, encodes a variant of paraplegin targeted to the endoplasmic reticulum. PLoS ONE 2012;7(5):e36337.

Michał J Okoniewski and Crispin J Miller. Comprehensive Analysis of Affymetrix Exon Arrays Using BioConductor. PLoS Comput Biol. 2008;4(2):e6.

Zaharieva E, J, Chipman JK, Soller M. Alternative splicing interference by xenobiotics. Toxicology 2012;296(1-3).

Journal Articles: 11 Displayed | Download in RIS Format

Publications Views

Other center views:	All 73 publications	15 publications in selected types	All 11 journal articles

Publications

Type	Citation	Sub Project	Document Sources
Journal Article	Gerona RR, Woodruff TJ, Dickenson CA, Pan J, Schwartz JM, Sen S, Friesen MW, Fujimoto VY, Hunt PA. Bisphenol-A (BPA), BPA glucuronide, and BPA sulfate in midgestation umbilical cord serum in a northern and central California population. Environmental Science & Technology 2013;47(21):12477-12485.	R834678C001 (Final) R834678C003 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Abstract: ACS Publications-Abstract Exit
Journal Article	Robinson J, Hamilton E, Lam J, Chen H, Woodruff T. Differences in cytochrome p450 enzyme expression and activity in fetal and adult tissues. PLACENTA 2020;100:35-44.	R834678 (Final) R835433 (Final)	Full-text from PubMed Associated PubMed link Full-text: ScienceDirect - Full Text HTML Exit Other: ScienceDirect - Full Text PDF Exit
Journal Article	Sutton P, Giudice LC, Woodruff TJ. Reproductive environmental health. Current Opinion in Obstetrics and Gynecology 2010;22(6):517-524.	R834678 (2012)	Abstract from PubMed Abstract: LWW-Abstract Exit
Journal Article	Sutton P, Woodruff TJ, Vogel S, Bero LA. Conrad and Becker's "10 Criteria" fall short of addressing conflicts of interest in chemical safety studies. Environmental Health Perspectives 2011;119(12):A506-507.	R834678 (2010) R834678 (2011)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: EHP-Full Text HTML Other: EHP-Full Text PDF
Journal Article	Sutton P, Wallinga D, Perron J, Gottlieb M, Sayre L, Woodruff T. Reproductive health and the industrialized food system: a point of intervention for health policy. Health Affairs 2011;30(5):888-897.	R834678 (2010) R834678 (2011) R834678 (2012)	Abstract from PubMed Full-text: Health Affairs-Full Text HTML Exit Abstract: Health Affairs-Abstract Exit Other: Health Affairs-PDF Exit
Journal Article	Sutton P, Woodruff TJ, Conry J, Giudice LC. Toxic matters and fertility: what can a doctor do? San Francisco Medicine: Journal of the San Francisco Medical Society 2012;85(5)20-22.	R834678 (2012)	Other: SFMS-PDF of Entire Issue Exit
Journal Article	Sutton P, Woodruff TJ, Perron J, Stotland N, Conry JA, Miller MD, Giudice LC. Toxic environmental chemicals: the role of reproductive health professionals in preventing harmful exposures. American Journal of Obstetrics and Gynecology 2012;207(3)164-173.	R834678 (2010) R834678 (2011) R834678 (2012)	Full-text from PubMed Abstract from PubMed Associated PubMed link Abstract: AJOG-Abstract Exit Other: ScienceDirect-Abstract Exit
Journal Article	Sutton P, Woodruff TJ. Risk communication and decision tools for children's health protection. Birth Defects Research Part C: Embryo Today: Reviews 2013;99(1):45-49.	R834678 (2012)	Abstract from PubMed Abstract: Wiley Online-Abstract Exit Other: ResearchGate-Abstract Exit
Journal Article	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.).	R834678C001 (Final) R835436 (2014) R835436 (2015) R835436 (2017)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: BioMed Central-Full Text HTML Exit Other: BioMed Central-Full Text PDF Exit
Journal Article	Woodruff TJ, Sutton P, Navigation Guide Work Group. An evidence-based medicine methodology to bridge the gap between clinical and environmental health sciences. Health Affairs 2011;30(5):931-937.	R834678 (2010) R834678 (2011) R834678 (2012)	Abstract from PubMed Full-text: Health Affairs-Full Text HTML Exit Abstract: Health Affairs-Abstract Exit Other: Health Affairs-PDF Exit
Journal Article	Woodruff TJ, Burke TA, Zeise L. The need for better public health decisions on chemicals released into our environment. Health Affairs 2011;30(5):957-967.	R834678 (2011)	Abstract from PubMed Full-text: Health Affairs-Full Text HTML Exit Abstract: Health Affairs-Abstract Exit Other: Health Affairs-Full Text PDF Exit

Supplemental Keywords:

Risk assessment, metabolism, bioavailability, ethnic groups, endocrine disruptors, sensitive populations, decision making, measurement methods, pre-mRNA splicing, Navigation Guide, preconception, prenatal, RFA, Scientific Discipline, Health, Health Risk Assessment, Biochemistry, Children's Health, Biology, prenatal exposure, biological response, assessment of exposure

Relevant Websites:

UCSF Program om Reproductive Health and the Environment Exit
Information for Families: Toxic Matters Exit

Progress and Final Reports:

Original Abstract

2010 Progress Report

2011 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).
R834678C001 Assessing Maternal and Fetal Exposure to Chemicals
R834678C002 Assessing the Effects of BPA Exposure on Early Human Development
R834678C003 (Pilot Study): Predictors of Maternal Exposure to BPA During Pregnancy