Grantee Research Project Results
2015 Progress Report: The UCSF Pregnancy Exposures to Environmental Chemicals (PEEC) Children's Center
EPA Grant Number: R835433Center: Center for Integrative Research on Childhood Leukemia and the Environment - 2015
Center Director: Metayer, Catherine
Title: The UCSF Pregnancy Exposures to Environmental Chemicals (PEEC) Children's Center
Investigators: Woodruff, Tracey J. , Gould, Robert , Fisher, Susan J. , Zlatnik, Marya , McMaster, Michael , Stotland, Naomi , Sutton, Patrice , Morello-Frosch, Rachel , Gerona, Roy , Sen, Saunak
Current Investigators: Woodruff, Tracey J.
Institution: University of California - San Francisco
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, 2015 through May 31,2016
Project Amount: $3,312,848
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:
Project 1: Modeling the Effects of EDCs on Early Stages of Human Placental Development
The hypothesis of our PEEC Children’s Center is that environmental chemical exposures have harmful effects on human in utero development and on children’s health. Project 1 brings together a team of basic scientists who are investigating the impact of brominated diphenyl ether‐47 (BDE‐47), a flame retardant, and perfluorooctanoic acid (PFOA), a repellent, on formation of the human placenta. The goal of the project is to map, at high resolution, the effects of these chemicals on the transcriptome (Aim 1), the epigenome (Aim 2) and the functional consequences of the alterations we observe (Aim 3). In Aim 1, we will use our in vitro model of human placentation and an unbiased approach, RNA‐seq, to understand the pathways in which BDE‐47 and/or PFOA are working in terms of effects on trophoblast function. Aim 2 uses the same experimental design to carry out a comprehensive analysis of the effects of these chemicals on histone modifications and DNA methylation. Finally, in Aim 3, we will study the functions of molecules that are targets of the environmental chemicals of interest and which we suspect play important roles in human placental development. These experiments will employ functional and molecular analyses that will allow us to phenotype human trophoblast cells and their defining properties in relation to environmental chemical exposures.
Project 2: Mid-Gestational Exposure to EDCs and Effects on Placental Development
Our project tests the hypotheses that 1) polybrominated diphenyl ethers (PBDEs), perfluorinated chemicals (PFCs), and select environmental organic acids (EOAs) accumulate differently in human fetuses than in pregnant women during the 2nd trimester of pregnancy, and 2) these chemical exposures negatively impact placental development and function, an important outcome that can adversely affect in utero growth, prenatal development, birth weight, and thus, childhood and adult health. Compelling scientific data show that human in utero development is highly susceptible to disruption by exposure to chemicals, in particular endocrine disrupting agents, but a major impediment to understanding these risks is the lack of human data on fetal exposures and on the mechanisms by which chemicals can adversely impact in utero development. Through our work as a Formative Center, we provided some of the first human data characterizing mid-gestation chemical exposures and mechanisms of adverse effects.
Specifically, we detected PBDEs, PFCs and EOAs such as Bisphenol-A (BPA) in 99-100% of the pregnant women and 95- 100% of fetuses (liver and umbilical cord blood) in our study population. In addition, in vitro experiments that employed our novel human trophoblast progenitor cell (TBPC) model of placental development demonstrated that environmentally relevant doses of PBDE-47 (a PBDE congener) compromised TBPC self-renewal in an undifferentiated state while promoting differentiation (see Project 1, Aim 1). Both effects are hallmarks of poor placental development and have been shown to be risk factors for reduced fetal growth, preterm delivery and preeclampsia. Our project will significantly advance this promising line of research to include a larger sample size, a more diverse set of biological specimens and a wider range of measured chemicals. We will also test the impact of these chemicals on in utero development by assessing the relationship between direct measures of chemical exposure and morphological and molecular markers that enable an assessment of placentation. Accordingly, our specific aims are to:
Aim 1: Compare maternal serum, placenta and fetal liver levels of a broad range of chemicals through traditional and novel biomonitoring approaches. We will collect matched biological specimens from 130 pregnant women obtaining elective 2nd trimester pregnancy terminations (excluding cases in which pregnancies are complicated by fetal anomalies or maternal smoking). We will analyze the samples for 17 PBDEs and 12 PFCs. We will also use a novel biomonitoring approach based on Time-of-Flight Liquid Chromatography-Mass Spectrometry (LC-QTOF/MS) combined with traditional analytic methods to identify and quantify exposure to the 5 most frequently detected EOAs in our study population. We will compare measurements of these 34 chemicals in maternal serum to those in the placenta and fetal liver. Thus, at the conclusion of these experiments we will have a much broader understanding of the most significant environmental chemical exposures during pregnancy and the relationships between levels detected in the maternal blood, placenta and fetus.
Aim 2: Evaluate the relationship between placental disruption and exposure to PBDEs, PFCs and select EOAs. We will measure known morphological and molecular markers of placenta development in the 2nd trimester placentas that are collected in Aim 1. Then we will evaluate the relationship of these markers to individual and cumulative metrics of PBDE, PFC and EOA exposure measured in the same placental samples. Additionally, the goal of Project 1 is to identify novel PBDE and PFC placental targets (specifically, PBDE-47 and PFOA, respectively). In Aim 3 of that Project, we will also evaluate the relationship between these endpoints, which will be analyzed in the same placental samples, and individual and cumulative metrics of PBDE, PFC and EOA exposure. Thus, at the conclusion of these experiments we will have important new information about the placental effects of endocrine disrupting chemicals.
Working with our Community Outreach and Translation Core, we will translate our findings to the clinical and policy communities, thus providing key inputs for improving public policy approaches to identifying, assessing and preventing human risks from these endocrine disrupting chemicals.
Project 3: Effects of EDCs and Chronic Psychosocial Stress on Fetal Growth
This project will examine the hypothesis that prenatal exposures to endocrine disrupting chemicals (EDCs) affect fetal growth outcomes such as birth weight and small for gestational age (SGA), and whether these adverse effects are magnified by chronic psychosocial stress. We will conduct a prospective study in an economically and ethnically diverse group of pregnant women in order to evaluate two important types of environmental exposures: 1) EDCs - polybrominated diphenyl ethers (PBDEs) and perfluorinated chemicals (PFCs); and 2) chronic psychosocial stress, using objective and subjective measures of participants’ perceived stress, social standing, physical and social environments, and biomarkers of chronic stress response. We hypothesize that exposure to both EDCs and stress may have synergistic effects on fetal growth. Accordingly, this project has three specific aims:
Aim 1: Evaluate the relationship between prenatal PBDE and PFC exposures and birth weight. Hypothesis: Higher levels of PBDEs and PFCs in maternal serum are independently associated with lower birth weight and SGA, and concurrent exposures to these two classes of compounds have cumulative effects on birth weight. We will measure PBDEs and PFCs in serum from pregnant women (N=450) during their second trimester and collect demographic, pregnancy history, and birth outcome data at delivery to analyze the following outcomes: 1) birth weight, 2) low birth weight (less than 2500 grams), and 3) SGA (birth weight less than the 10th percentile for the infant’s gestational age based on growth curves accounting for race/ethnicity and sex).
Aim 2: Evaluate the relationship between measures of chronic psychosocial stress in the maternal-fetal unit and birth weight outcomes. Hypothesis: Exposures to chronic stress is associated with lower birth weight and SGA. We will collect three types of chronic stress measurements: 1) Metrics based on participants’ perceptions of their social standing and their chronic stress exposures in household, neighborhood, and work environments; 2) geocoded metrics of neighborhood socioeconomic status and civic engagement capacity; and 3) biological markers of chronic stress response in the maternal-fetal unit, including telomere length in umbilical cord leukocytes and corticotropin releasing hormone (CRH) levels in maternal plasma. We will examine whether fetal and maternal biomarkers of stress response mediate the relationship between perceptual and geocoded measures of chronic stress exposure and adverse birth weight effects.
Aim 3: Assess whether exposure to chronic psychosocial stress in the maternal-fetal unit modifies the relationship between PBDE and PFC exposures and birth weight outcomes. Hypothesis: The effects of prenatal PBDE and PFC exposures on birth weight are modified by exposure to chronic stress in the maternal-fetal unit. We will evaluate potential interactions between the chemical exposures and chronic stress exposure on birth weight. Our approach to modeling chemical and chronic stress exposures will be informed by our analytical results from Aims 1 and 2. The ethnic and economic diversity of our study population will provide a unique advantage for enhancing scientific understanding about the range of prenatal exposures to persistent and ubiquitous EDCs and their effects on fetal growth.
Community Outreach and Translation Core
Aim 1: Communicate the Science Broadly
Aim 2: Harness the Evolving Science to Healthcare
Aim 3: Advance Prevention‐Based Public Policy
Progress Summary:
Project 1: Modeling the Effects of EDCs on Early Stages of Human Placental Development
During the third project period, we continued to make progress on Aims 1 and 2 using human villous cytotrophoblast (CTB) cells, a model system in which we have over 20 years of experience, to study placentation in normal pregnancy and in pregnancy complications. We selected this primary placental cell model to leverage recently generated transcriptomic and epigenomic data due to our participation in the NIH-funded Roadmap Epigenome Mapping Center (Kundaje, et al., 2015). From these analyses, we gained a unique understanding of the transcriptomic and epigenetic landscape of CTBs and other extraembryonic tissues in vivo under normal physiological conditions. This information provided a baseline for understanding molecular perturbations that may result from environmental chemical exposure(s), the goal of this project.
With regard to Aims 1 and 2, we conducted transcriptomic and methylation analyses of the effects of BDE-47 exposure in our CTB model system. Based on our dose/time response investigations completed in Years 1 and 2, which established relevant timing and dosage parameters in our model, we designed these experiments to include: 1) a sub-cytotoxic concentration of BDE-47 (1 μM), which was biologically effective in our model system and relevant to human exposures; and 2) two exposure windows of interest in cultured CTBs, which paralleled significant dynamic changes in cell migratory activity and expression of genes linked to morphogenesis, cell motility, and vascular remodeling pathways. These fundamental cellular and molecular processes are hypothesized to underlie the critical functions of CTBs in vivo, such as uterine invasion, vascular remodeling, and establishing physical and physiological connections between the placenta and uterus. We evaluated the effects of BDE-47 after 24h of exposure based on our dose/time-response investigations in Year 1, and previous reports suggesting that PBDEs alter gene/protein expression in trophoblast cell lines after 24h of exposure (Park, et al., 2014).
For these analyses, we collected RNA/DNA samples simultaneously from 3 independent cultures of 2nd trimester human CTBs, which were exposed to either BDE-47 (1 μM) or vehicle control (1% DMSO; 12 samples for each analysis). To globally profile gene expression, we used Affymetrix GeneChip Human Gene 2.0 ST Arrays. Sample processing and hybridization was performed by the UCSF Gladstone Institute. Following data normalization, we applied a fixed effects linear model (ANOVA) to determine differentially expressed (DE) genes due to BDE-47 exposure, culture time, and gestational age. Our previous transcriptomic analyses of (unexposed) cultured CTBs (Robinson, et al., manuscript submitted) suggest that time in culture and gestational age influences the expression of hundreds of genes that are important for placental development and function. Therefore, we used a statistical approach that controls for these variables.
The analysis included CTBs purified from 3 placentas. We identified 433 genes as significantly differentially expressed (DE) due to BDE-47 exposure (ANOVA: p ≤ 0.025, absolute FC > 1.25). In general, transcriptional changes after 24h of exposure were similar regardless of whether the chemicals were added 3 or 15h post-plating. Regarding the two exposure windows, 92% of DE genes trended the same. In total, with BDE-47 exposure, 230 genes (53%) were upregulated (Cluster I) and 203 (47%) were downregulated (Cluster II). We performed functional enrichment analysis of Gene Ontology (GO) Biological Processes within the complete set of genes altered by BDE-47 as well as analyses of up (Cluster I) and down-regulated (Cluster II) subsets. We observed significant enrichment of GO terms, including: Organ Development, Steroid Hormone Response, Regulation of Cell Proliferation, Regulation of Programmed Cell Death, Angiogenesis, Regulation of Inflammatory Response, Chemical Homeostasis, and Neuron Development (enriched in Cluster I); and Steroid Metabolic Process, Sterol Transport, Hydrolase Activity, Immune Process, and Carbohydrate Metabolism (enriched in Cluster II). Inflammatory and neuron differentiation-related gene pathways were also altered following exposures to PBDEs in other models (Slotkin, et al., 2013; Park, et al., 2014). In addition, we identified numerous novel targets of this compound.
Next, we evaluated the effects of five concentrations of BDE-47 (0.1-10 μM) on specific DE targets, using qRT-PCR to verify our microarray results and interrogate the dose-response relationship between exposure and expression. For this purpose, we prepared RNA samples from CTBs that were isolated from ≥ 3 additional placentas. We confirmed DE of nine targets, eight of which had significant monotonic dose-response relationships with BDE-47 exposure (ANOVA, p < 0.05). We observed significant upregulation of IL6, MMP1, GREM1, FABP4, and PLAC4; and downregulation of GPR34, SCD, HMGCS1 and FABP7 with BDE-47. These validated targets are key members of diverse functional pathways that are involved in different aspects of placental development, including trophoblast differentiation, inflammation, fatty acid metabolism, steroid metabolism and morphogenesis. For example, BDE-47 altered the expression of MMP1, an enzyme involved in extracellular matrix breakdown/trophoblast invasion (Cohen, et al., 2006), and implicated, at a mechanistic level, in preeclampsia (PE) (Lian, et al., 2010) and preterm birth (Sundrani, et al., 2012). The cAMP-regulated and placenta-specific gene family member, PLAC4, has also been linked with trophoblast invasion and may be a biomarker of severe early onset PE (Tuohey, et al., 2013). Fatty acid (FA) binding proteins, FABP4 and FABP7, have diverse functions in uptake, transport, and metabolism of FAs and hydrophobic ligands. While their roles in placenta development remain undefined, emerging studies also suggest potential links to PE (Yan, et al., 2016). Interleukins and other inflammatory mediators e.g., cytokines, control interactions between hemi-allogeneic CTBs and the maternal immune cells with which they come into contact (Librach, et al., 1994). In this regard, BDE-47 also upregulated expression of IL-6. These findings agree with a recent in-depth analysis of BDE-47 in the HTR-8/SVneo trophoblast cell line where expression of inflammatory (IL-6, -8) and oxidative stress mediators was induced (Park, et al., 2014).
In summary, our transcriptomic results suggested that BDE-47, in a concentration dependent manner, perturbs known and previously unknown pathways critical for trophoblast function and placental development. We presented these initial transcriptomic analyses in an abstract entitled, "Gene Expression Profiling: The Effects of BDE-47 on Human Primary Cytotrophoblasts" at the Society of Toxicology Annual Meeting in New Orleans, LA in (March, 2016). Investigations that build on these findings (see Section 3) include evaluating expression of these markers, at the protein level, by using an immunofluorescence approach applied to 2nd trimester placental biopsies from pregnancies in which maternal blood levels of the BDE congeners had been measured (Project 2). Using molecules identified in this subset, we will conduct functional studies to determine the relevance of specific gene-environment interactions in our CTB model (Aim 3).
For our initial epigenomic analyses, we measured global methylation using Illumina Infinium HumanMethylation450 BeadChip arrays. This approach enabled us to investigate methylation levels for ~99% of genes and ~96% of CpG islands in the human genome. All data were processed using a state-of-the-art pipeline developed in Dr. Costello's laboratory, which includes methylumi background correction and normalization operations. Currently, we are finalizing our transcriptomic data analyses, which will enable us to pinpoint the specific targets altered by BDE-47. Within regulatory regions (e.g., promoters) of this gene subset, we will conduct a focused analysis of methylation levels between the BDE-47 and vehicle control exposure groups. Overall, these -omic studies will inform the design of experimental design of future, more resource-intensive investigations.
To increase the utility of our CTB model for environmental investigations, we are also developing high-throughput functional tests to evaluate their migratory activity in our culture system. In vivo, CTB invasion begins as the cells migrate toward one another and away from the placenta. Using a semi-automated protocol—which includes nuclear staining (Hoescht), the capture of multiple images (Leica), and image content analysis (Volocity)—we can analyze hundreds of thousands of CTBs across multiple time points in vitro. In unexposed cultures, significant migratory activity occurs within the first 39h of culture. Currently, we are using this assay system to test the effects of BDE-47. This assay, in combination with methods we use to analyze other parts of the invasion process, could build mechanistic relationships between environmental exposures and CTBs behaviors that are highly relevant to placentation in vivo.
This project continues to provide significant professional development opportunities for a Postdoctoral Fellow in the laboratory, Dr. Joshua Robinson. He has been doing the human placental work alongside his K99/R00 Pathways to Independence project entitled, “Polybrominated Diphenyl Ether Effects on Human Neuronal Development.” His growing expertise in using in vitro model systems for studying the developmental effects (in humans) of gestational exposures to environmental chemicals is the direct result of participation in these projects. In addition, Emily Hamilton, a Research Associate and recent college graduate, worked with us part-time (shared with our P01 collaborator, Dr. Joe Costello). She assisted Dr. Robinson with qRT-PCR and immunolocalization analyses. This fall she is starting a PhD program (Cell and Molecular Biology) at Stanford. Her participation in this project furthered her scientific development on several levels and cemented her interest in human biology.
Project 2: Mid-Gestational Exposure to EDCs and Effects on Placental Development
With consultation from our Project Officers, we recently changed our specific aims to exclude the analysis of PFCs in tissue samples (placenta and fetal liver), which were included in the aims outlined in our grant application. The reason for this change is that the methods development for the PFCs took longer and more resources than anticipated and we have not observed significant responses to PFOA in our in vitro placental cell system. Thus, in order to meet our project timelines and based on our in vitro findings, we will concentrate our efforts on PBDEs and EOAs analyses in maternal and fetal tissue, and PFCs in maternal serum.
We have achieved a number of accomplishments for Project 2 in project year 3.
We completed recruitment in January 2016 in the Women’s Options Center at San Francisco General Hospital. We have collected 133 matched sets of maternal serum, fetal liver, and placenta. Placenta samples have been fixed in formalin for future immunohistochemistry analyses. Based on findings in project 1, which evaluated the effects of BDE-47 on functional and transcriptomic levels in 2nd trimester human primary cytotrophoblasts, potential biomarkers of PBDE exposure have been identified. For a subset of these targets, validation studies have been conducted to verify differential expression due to PBDE exposure in vitro. Following these studies, for two of these targets, MMP1 and GREM1, we have identified the positive presence of protein expression in our cytotrophoblast cultures and in a subset of pilot 2nd trimester placental samples (within the basal plate, where we can examine the expression of these markers in invading trophoblast populations) using specific antibodies. We will analyze the expression of MMP1 and GREM1 in placental samples through FY4 using immunohistochemistry-based approaches.
Methods for PBDE analysis in serum and liver have been developed by our collaborators at California Department of Toxic Substances (DTSC), Drs. Myrto Petreas and June‐ Soo Park. Methods development for PBDE analysis in placenta has been finalized. In addition, we have started PBDE chemical analysis on liver and serum and have preliminary data on 59 study participants. PBDE analysis will continue through FY4.
The method for PFCs analysis in serum was completed by Dr. Roy Gerona at UCSF Department of OB/Gyn and Reproductive Sciences in Year 3. PFC analysis in maternal serum will be complete in the first quarter of Year 4. In addition, Dr. Roy Gerona has completed methods for non‐targeted analysis of EOAs in serum using LC‐QTOF/MS, and has a draft manuscript in progress for publication.
Project 3: Effects of EDCs and Chronic Psychosocial Stress on Fetal Growth
Fund Year 3 (FY) was spent continuing to recruit participants at San Francisco General Hospital (SFGH), and the Betty Irene Moore Women’s Health Hospital at Mission Bay (MB). Currently recruitment and study visits take place at SFGH and MB, although we do some 2nd trimester participant visits at Moffitt Long Hospital at Parnassus.
We have enrolled a diverse sample of 306 participants (see Table 1) at a rate of approximately 10 participants per month. This enrollment rate is lower than we expected due to the hospital move in January of 2015, a pause in recruitment due to a change in the medical record keeping at SFGH to an electronic system, and due to personnel changes that continued in FY3. To address these challenges we hired more research staff for recruitment and made some changes to our protocol to increase our enrollment rate. Specifically, we increased our staffing effort by .1 FTE in June 2015 and an additional .5 FTE in February 2016. As a result, we have started to see a significant uptick in our enrollment rates and anticipate that in Year 4 we will be able recruit approximately four participants per week (or 16 per month) due to the increase in staff FTE.
Table 1: Demographics of CIOB2 Study Participants |
||
Race |
n |
% |
Asian/PI |
49 |
18 |
AA/Black |
28 |
10 |
Caucasian/White |
113 |
41 |
Native American |
2 |
1 |
Other |
78 |
28 |
Don't Know |
6 |
2 |
Hispanic/Latina |
n |
% |
Yes |
85 |
31 |
No |
184 |
68 |
Don't Know |
7 |
3 |
Education |
n |
% |
Less than High School |
32 |
12 |
High School/GED |
41 |
15 |
Some College/AA |
34 |
13 |
Bachelor's Degree |
57 |
21 |
Master's Degree |
55 |
20 |
Doctoral Degree |
51 |
19 |
Don't Know |
7 |
3 |
Income |
n |
% |
<$20k |
14 |
5 |
$20k<$100k |
70 |
26 |
$100k<$200k |
73 |
27 |
>$200k |
57 |
21 |
Don't Know |
8 |
3 |
PBDE methods development in serum by our collaborators at California Department of Toxic Substances Drs. Myrto Petreas and June-Soo Park is complete. Dr. Roy Gerona at UCSF Department of Clinical Toxicology has finalized methods for PFC analysis in serum. Methods for CRH analysis was completed by the Fisher lab and telomere analysis will begin at the middle of Year 4 by the Blackburn lab. In addition, we will begin preliminary analysis of chemical compounds at the mid-point of Year 4.
In addition, we have collected 124 3rd trimester maternal blood samples and 113 cord blood samples to date and are expecting to begin CRH and telomere analyses in the 4th quarter of FY3, continuing in FY4.
We received an administrative supplement which has allowed us to begin collecting placentas at delivery for analysis with our collaborators at the Fisher lab. The goal of this pilot project is to collect 50 placentas to generate preliminary data on biomarkers of relevance to placental development. Collection began in February 2016 and to date we have collected 16 placentas from our participants.
Community Outreach and Translation Core
Aim 1: Communicate the Science Broadly
We distributed 2,500 hard copies of our All That Matters series of patient‐centered brochures; updated and translated into Spanish our entire series of All That Matters, including Toxic Matters, Work Matters, Pesticides Matter, and What To Eat; every week someone from our PEEC Center was making a presentation about toxic chemicals; we conducted 35 presentations related to the health impacts of exposure to toxic environmental chemicals and the need to improve public policy in a wide range of venues, and reaching a wide range of audiences, primarily health professionals, scientists, policy makers, medical and public health students, government and advocates, and the public; used Facebook and Twitter to communicate the science approximately 3 or more times per week; obtained funding to expand our partnership with a health educator/product developer (SafetyNEST) who is transforming the content of our All That Matters series of patient centered brochures into a mobile app; communicated the International Federation on Gynecology and Obstetrics (FIGO) Opinion on reproductive health impacts of environmental chemicals, which produced coverage in over 50 news outlets, including newspapers, radio interviews, and blogs, including but not limited to the U.K, U.S., Canada, France, Africa, Asia, and Japan; and in publications such as the New York Times, Huffington Post, Mother Jones, FOX news, and the “Gupta Guide.” Our social media outreach at #healthnottoxics went viral. We also published two blogs about the Opinion in Health Affairs and on the Collaborative of Health and the Environment. In addition to FIGO, we were quoted in 15 print or online media outlets.
Aim 2: Harness the Evolving Science to Healthcare
We catapulted the momentum created in 2013 when U.S. OBGYNs called for action on toxic chemicals into a global demand by reproductive health professionals for prevention-oriented action. Reproductive health professional societies around the globe now regard the topic of preventing exposure to toxic chemicals as their issue. We led the collaborative process that led to the publication in October 2015 of the FIGO Opinion on Reproductive Health Impacts of Exposure to Toxic Environmental Chemicals. FIGO is the leading voice of reproductive health professionals around the world and its actions have global resonance. FIGOs member organizations include 125 countries/territories. The FIGO Opinion, which leveraged the science produced by 11 Children’s Centers, and was endorsed by 12 other reproductive health professional societies, recommends that reproductive and other health professionals advocate for policies to prevent exposure to toxic environmental chemicals, work to ensure a healthy food system for all, make environmental health part of health care, and champion environmental justice. We also organized a global Summit of OBGYNs to set an agenda for action on reproductive environmental health, held on October 4, 2015, immediately prior to the beginning of the FIGO XXI World Congress in Vancouver, Canada. The Summit brought together 50 leaders of reproductive health professional societies from 22 countries across the globe who developed a plan of action to address the global threat of environmental chemicals to reproductive health. The recommendations from the Summit now serve as a starting point for the newly formed FIGO Reproductive Developmental Environmental Health (RDEH) Work Group. The RDEH will carry the action plan forward with its inaugural meeting in December of 2016, which Dr. Woodruff will be attending. Almost 7,000 people from 143 countries attended the FIGO XXI World Congress, providing a large audience for presentations, extensive networking opportunities at our booth in the exhibition hall and at throughout the Congress, as well as through social media. We organized and recorded the FIGO plenary and scientific session on reproductive environmental health and posted them on UCTV and NextGenU Environmental Health course for wide dissemination (http://www.uctv.tv/shows/Environmental-Exposures-Reproductive-Outcomes-A-Call-to-Action-International-Federation-of-Gynecology-and-Obstetrics-FIGO-XXI-World-Congress-Symposium-29974). We have had 398 views on YouTube. We also organized an elective course on environmental health including health care institutional sustainability issues. Dr. Woodruff also served as faculty for a required course for 2nd year medical students; we served on the UCSF Sustainability Committee; and from June 2015 to July 2016, PRHE’s Natalyn Daniels served on the Reproductive Health and the Environment Conference Planning Committee for the UCLA Iris Cantor Women’s Health Center, and Dr. Marya Zlatnik was the 2016 plenary speaker.
Aim 3: Advance Prevention‐Based Public Policy
We advanced uptake of the Navigation Guide systematic review methods through 5 meetings and briefings with decision‐makers in key federal and state agencies, including with key governmental and clinical organizational leaders; Held 3 Navigation Guide Work Group Webinars; Published our third case study on applying the Navigation Guide methodology; completed two additional case studies; and secured funding for a sixth case study on formaldehyde and asthma which is currently underway. Dr. Woodruff attended the GRADE Environmental Health Working Group meeting, which included government, academic, nonprofit, and other agencies around the world that gathered to discuss new tools, methods, and topics related to evidence integration and systematic review. The Navigation Guide method informed the development of the method now used by the National Toxicology Program for its decision-making about reproductive and developmental health hazards of environmental chemicals; as well as the method proposed by the European Union for its hazard and risk assessment of endocrine disrupting chemicals. These are critical outcomes as the decision-makers of all stripes rely on the authoritative lists of chemical hazards developed by these and other government agencies when making decisions about detoxifying our homes and communities.
Future Activities:
Project 1: Modeling the Effects of EDCs on Early Stages of Human Placental Development
At the beginning of year 4, we will continue with the analyses of the data that we have already obtained on the transcriptomic and epigenomic effects of BDE-47 exposure of CTBs. In independent cultures, we will confirm differentially expressed targets due to PBDE exposures, at protein and epigenome levels, in a dose-dependent manner. Examples of targets to be examined further include MMP1 and PLAC4. Using our methylation data, we plan to conduct focused assessments of promoter regions of genes that are significantly altered by BDE-47 with the goal of identifying possible alterations in their epigenetic marks. We will summarize these findings and use this information to inform the design of the next stage of experiments. As we coalesce datasets, we will choose the targets on which the functional analyses will concentrate (Aim 3). Additional studies, examining PFOA and other PBDE congeners, will be considered. We plan to submit a manuscript that summarizes the data contained in this progress report.
Project 2: Mid-Gestational Exposure to EDCs and Effects on Placental Development
In the next reporting period we will continue to measure PFCs in maternal serum, PBDEs in matched samples of maternal serum, fetal liver and placenta, conduct non-targeted analysis of EOA's in matched samples, and morphological and molecular assessment of placenta samples. Data analysis and manuscript preparation will be ongoing through Year 4.
Project 3: Effects of EDCs and Chronic Psychosocial Stress on Fetal Growth
We will continue to enroll participants each week from each study site (SFGH and Mission Bay), and finish enrollment by the end of Year 4. Also, chemical analyses for PBDEs and PFCs have commenced and should be completed by the first quarter of Year 5. We expect to finalize stress biomarker analysis (telomeres and CRH) during mid FY 5.
Community Outreach and Translation Core
Continued advancement of our aims, including participation in the FIGO RDEH Working Group; embedding environmental health in medical education at UCSF and beyond; communications and dissemination of the science through print, electronic, and social media, and outreach and education to health professionals and decision-makers; completion and dissemination of our case studies of applying the Navigation Guide systematic review methodology; dissemination of our All That Matters patient centered educational materials including completion of the SafetyNEST app version 1.0.
References:
Cohen, M., A. Meisser, et al. (2006). "Metalloproteinases and human placental invasiveness." Placenta 27(8): 783-793.
Kundaje, A., W. Meuleman, et al. (2015). "Integrative analysis of 111 reference human epigenomes." Nature 518(7539): 317-330.
Lian, I. A., J. H. Toft, et al. (2010). "Matrix metalloproteinase 1 in pre-eclampsia and fetal growth restriction: reduced gene expression in decidual tissue and protein expression in extravillous trophoblasts." Placenta 31(7): 615-620.
Librach, C. L., S. L. Feigenbaum, et al. (1994). "Interleukin-1 beta regulates human cytotrophoblast metalloproteinase activity and invasion in vitro." The Journal of biological chemistry 269(25): 17125-17131.
Park, H. R., P. W. Kamau, et al. (2014). "Involvement of reactive oxygen species in brominated diphenyl ether-47-induced inflammatory cytokine release from human extravillous trophoblasts in vitro." Toxicology and applied pharmacology 274(2): 283-292.
Park, H. R. and R. Loch-Caruso (2014). "Protective effect of nuclear factor E2-related factor 2 on inflammatory cytokine response to brominated diphenyl ether-47 in the HTR-8/SVneo human first trimester extravillous trophoblast cell line." Toxicology and applied pharmacology 281(1): 67-77.
Slotkin, T. A., J. Card, et al. (2013). "BDE99 (2,2',4,4',5-pentabromodiphenyl ether) suppresses differentiation into neurotransmitter phenotypes in PC12 cells." Neurotoxicology and teratology 37: 13-17.
Sundrani, D. P., P. M. Chavan-Gautam, et al. (2012). "Matrix metalloproteinase-1 and -9 in human placenta during spontaneous vaginal delivery and caesarean sectioning in preterm pregnancy." PloS one 7(1): e29855.
Tuohey, L., K. Macintire, et al. (2013). "PLAC4 is upregulated in severe early onset preeclampsia and upregulated with syncytialisation but not hypoxia." Placenta 34(3): 256-260.
Yan, Y., H. Peng, et al. (2016). "Increased expression of fatty acid binding protein 4 in preeclamptic Placenta and its relevance to preeclampsia." Placenta 39: 94-100.
Journal Articles: 48 Displayed | Download in RIS Format
Other center views: | All 77 publications | 54 publications in selected types | All 48 journal articles |
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Type | Citation | ||
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Abrahamsson D, Park J, Singh R, Sirota M, Woodruff T. Applications of Machine Learning to In Silico Quantification o Chemicals without Analytical Standards. Journal of Chemical Information and Modeling 2020;60(6):2718-2727. |
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Abrahamsson D, Siddharth A, Young T, Sirota M, Park J, Martin J, Woodruff T. In Silico Structure Predictions for Non-targeted Analysis: From Physicochemical Properties to Molecular Structures. JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMOTY 2022;33(7):1134-1147 |
R835433 (Final) |
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Abrahamsson D, Brueck C, Prasse C, Lambropoulou D, Koronaiou L, Wang M, Park J, Woodruff T. Extracting Structural Information from Physicochemical Property Measurements Using Machine Learning-A New Approach for Structure Elucidation in Non-targeted Analysis. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2023;27(40):14827-14838 |
R835433 (Final) R835643 (Final) |
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Bland G, Abrahamsson D, Wang M, Zlatnik M, Morello-Frosch R, Park J, Sirota M, Woodruff T. Exploring applications of non-targeted analysis in the characterization of the prenatal exposome. SCIENCE OF THE TOTAL ENVRIONMENT 2023;912(169458) |
R835433 (Final) |
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Casey JA, Karasek D, Ogburn, EL, Goin DE, Dang K, Braveman PA, Morello-Frosch R. Coal and oil power plant retirements in California:association with reduced preterm birth among populations nearby. American Journal of Epidemiology 2018;187(8):1586-1594. |
R835433 (2017) R835433 (Final) |
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Casey JA, Gemmill A, Karasek D, Ogburn, EL, Goin DE, Morello-Frosch R. Increase in fertility following coal and oil power plant retirements in California. Environmental Health 2018;17(1):44 (10 pp.). |
R835433 (2017) R835433 (Final) |
Exit Exit |
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Di Renzo GC, Conry JA, Blake J, DeFrancesco MS, DeNicola N, Martin Jr. JN, McCue KA, Richmond D, Shah A, Sutton P, Woodruff TJ, van der Poel SZ, Giudice LC. International Federation of Gynecology and Obstetrics opinion on reproductive health impacts of exposure to toxic environmental chemicals. International Journal of Gynaecology and Obstetrics 2015;131(3):219-225. |
R835433 (2015) R835433 (Final) |
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Gerona RR, Pan J, Zota AR, Schwartz JM, Friesen M, Taylor JA, Hunt PA, Woodruff TJ. Direct measurement of bisphenol A (BPA), BPA glucuronide and BPA sulfate in a diverse and low-income population of pregnant women reveals high exposure, with potential implications for previous exposure estimates: a cross-sectional study. Environmental Health 2016;15:50 (14 pp.). |
R835433 (2015) R835433 (2017) R835433 (Final) |
Exit Exit |
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Gerona RR, Schwartz JM, Pan J, Friesen MM, Lin T, Woodruff TJ. Suspect screening of maternal serum to identify new environmental chemical biomonitoring targets using liquid chromatography-quadrupole time-of-flight mass spectrometry. Journal of Exposure Science & Environmental Epidemiology 2018;28(2):101-108. |
R835433 (2017) R835433 (Final) R835643 (2017) |
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Goin D, Abrahamsson D, Wang M, Jiang T, Park J, Sirota M, Morello-Frosch R, DeMicco E, Zlatnik M, Woodruff T. Disparities in chemical exposures among pregnant women and neonates by socioeconomic and demographic characteristics:A nontargeted approach. ENVIRONMENTAL RESEARCH 2022;215(1):114158. |
R835433 (Final) |
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Goin D, Abrhamsson D, Wang M, Park J, Sirota M, Morello-Frosch R, DeMicco E, Trowbridge J, Augt L, O'Connell S, Ladella S, Zlatnik M, Woodruff T. Investigating geographic differences in environmental chemical exposures in maternal and cord sera using non-targeted screening and silicone wristbands in California. JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY 2022;. |
R835433 (Final) |
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Huang H, Wang A, Morello-Frosch R, Lam J, Sirota M, Padula A, Woodruff TJ. Cumulative risk and impact modeling on environmental chemical and social stressors. Current Environmental Health Reports 2018;5(1):88-99. |
R835433 (2017) R835433 (Final) |
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Johnson PI, Sutton P, Atchley DS, Koustas E, Lam J, Sen S, Robinson KA, Axelrad DA, Woodruff TJ. The Navigation Guide—evidence-based medicine meets environmental health: systematic review of human evidence for PFOA effects on fetal growth. Environmental Health Perspectives 2014;122(10):1028-1039. |
R835433 (2014) R835433 (Final) |
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Johnson PI, Koustas E, Vesterinen HM, Sutton P, Atchley DS, Kim AN, Campbell M, Donald JM, Sen S, Bero L, Zeise L, Woodruff TJ. Application of the Navigation Guide systematic review methodology to the evidence for developmental and reproductive toxicity of triclosan. Environment International 2016;92-93:716-728. |
R835433 (2015) R835433 (2016) R835433 (Final) |
Exit Exit Exit |
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Koustas E, Lam J, Sutton P, Johnson PI, Atchley DS, Sen S, Robinson KA, Axelrad DA, Woodruff TJ. The Navigation Guide—evidence-based medicine meets environmental health:systematic review of nonhuman evidence for PFOA effects on fetal growth. Environmental Health Perspectives 2014;122(10):1015-1027. |
R835433 (2014) R835433 (Final) |
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Lam J, Koustas E, Sutton P, Johnson PI, Atchley DS, Sen S, Robinson KA, Axelrad DA, Woodruff TJ. The Navigation Guide—evidence-based medicine meets environmental health:integration of animal and human evidence for PFOA effects on fetal growth. Environmental Health Perspectives 2014;122(10):1040-1051. |
R835433 (2014) R835433 (Final) |
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Lam J, Lanphear BP, Bellinger D, Axelrad DA, McPartland J, Sutton P, Davidson L, Daniels N, Sen S, Woodruff TJ. Developmental PBDE exposure and IQ/ADHD in childhood: a systematic review and meta-analysis. Environmental Health Perspectives 2017;125(8):086001 (20 pp.). |
R835433 (2016) R835433 (2017) R835433 (Final) |
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Lam J, Kotas E, Sutton P, Padula A, Cabana M, Vesterinen H, Griffiths C, Dickie M, Daniels N, Whitaker E, Woodruff T. Exposure to formaldehyde and asthma outcomes:A systematic review, meta-analysis, and economic assessment. PLOS ONE 2021;16(3):e0248258. |
R835433 (Final) |
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Lam J, Sutton P, Kalkbrenner A, Windham G, Halladay A, Koustas E, Lawler C, Davidson L, Daniels N, Newschaffer C, Woodruff T. A Systematic Review and Meta-Analysis of Multiple Airborne Pollutants and Autism Spectrum Disorder. PLoS One. 2016 Sep 21;11(9):e0161851. doi:10.1371/journal.pone.0161851. PubMed PMID:27653281; PubMed Central PMCID:PMC5031428. |
R835433 (2016) R835433 (Final) |
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McHale CM, Osborne G, Morello-Frosch R, Salmon AG, Sandy MS, Solomon G, Zhang L, Smith MT, Zeise L. Assessing health risks from multiple environmental stressors: moving from G×E to I×E. Mutation Research 2018;775:11-20. |
R835433 (2017) R835433 (Final) |
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Morello-Frosch R, Cushing LJ, Jesdale BM, Schwartz JM, Guo W, Guo T, Wang M, Harwani S, Petropoulou SE, Duong W, Park J-S, Petreas M, Gajek R, Alvaran J, She J, Dobraca D, Das R, Woodruff TJ. Environmental chemicals in an urban population of pregnant women and their newborns from San Francisco. Environmental Science & Technology 2016;50(22):12464-12472. |
R835433 (2015) R835433 (2017) R835433 (Final) |
Exit Exit Exit |
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Morgan RL, Thayer KA, Bero L, Bruce N, Falck-Ytter Y, Ghersi D, Guyatt G, Hooijmans C, Langendam M, Mandrioli D, Mustafa RA, Rehfuess EA, Rooney AA, Shea B, Silbergeld EK, Sutton P, Wolfe MS, Woodruff TJ, Verbeek JH, Holloway AC, Santesso N, Schunemann HJ. GRADE: assessing the quality of evidence in environmental and occupational health. Environment International 2016;92-93:611-616. |
R835433 (2015) R835433 (2016) R835433 (Final) |
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Parry E, Zota AR, Park J-S, Woodruff TJ. Polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDE metabolites (OH-PBDEs): a six-year temporal trend in Northern California pregnant women. Chemosphere 2018;195-777-783. |
R835433 (2017) R835433 (Final) |
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Pelch K, Reade A, Kwiatkowski C, Merced-Nieves F, Cavalier H, Schultz K, Wolffe T, Varshavsky J. The PFAS-Tox Database:A systematic evidence map of health studies on 29 per-and polyfluoroalkyl substances. ENVIRONMENTAL INTERNATIONAL 2022;167(107408). |
R835433 (Final) |
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Roadmap Epigenomics Consortium, Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A, Kheradpour P, Zhang Z, Wang J, Ziller MJ, Amin V, Whitaker JW, Schultz MD, Ward LD, Sarkar A, Quon G, Sandstrom RS, Eaton ML, Wu YC, Pfenning AR, Wang X, Claussnitzer M, Liu Y, Coarfa C, Harris RA, Shoresh N, Epstein CB, Gjoneska E, Leung D, Xie W, Hawkins RD, Lister R, Hong C, Gascard P, Mungall AJ, Moore R, Chuah E, Tam A, Canfield TK, Hansen RS, Kaul R, Sabo PJ, Bansal MS, Carles A, Dixon JR, Farh KH, Feizi X, Karlic R, Kim AR, Kulkarni A, Li D, Lowdon R, Elliott G, Mercer TR, Naph SJ, Onuchic V, Polak P, Rajagopal N, Ray P, Sallari RC, Siebenthall KT, Sinnott-Armstrong NA, Stevens M, Thurman RE, Wu J, Zhang B, Zhou X, Beaudet AE, Boyer LA, De Jager PL, Farnham PJ, Fisher SJ, Haussler D, Jones SJ, Li W, Marra MA, McManus MT, Sunyaev S, Thomson JA, Tlsty TD, Tsai LH, Wang W, Waterland RA, Zhang MQ, Chadwick LH, Bernstein BE, Costello JF, Ecker JR, Hirst M, Meissner A, Milosavljevic A, Ren B, Stamatoyannopoulos JA, Wang T, Kellis M. Integrative analysis of 111 reference human epigenomes. Nature 2015;518(7539):317-330. |
R835433 (2014) R835433 (Final) |
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Robinson JF, Kapidzic M, Gormley M, Ona K, Dent T, Seifikar H, Hamilton EG, Fisher SJ. Transcriptional dynamics of cultured human villous cytotrophoblasts. Endocrinology 2017;158(6):1581-1594. |
R835433 (2016) R835433 (2017) R835433 (Final) |
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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. |
R835433 (Final) R834678 (Final) |
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Solomon GM, Morello-Frosch R, Zeise L, Faust JB. Cumulative environmental impacts: science and policy to protect communities. Annual Review of Public Health 2016;37:83-96. |
R835433 (2015) R835433 (2017) R835433 (Final) |
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Stotland NE, Sutton P, Trowbridge J, Atchley DS, Conry J, Trasande L, Gerbert B, Charlesworth A, Woodruff TJ. Counseling patients on preventing prenatal environmental exposures--a mixed-methods study of obstetricians. PLoS ONE 2014;9(6):e98771 (7 pp.). |
R835433 (2014) R835433 (Final) |
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Sutton PM, Giudice LC, Woodruff TJ. Moving from awareness to action on preventing patient exposure to toxic environmental chemicals. American Journal of Obstetrics and Gynecology 2016;214(5):555-558. |
R835433 (2015) R835433 (Final) |
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Sutton, P, Woodruff, TJ, Conry, J, Giudice, LC. Exposure to toxic chemicals:reproductive health professionals speak about the first 1,000 days. San Francisco Medicine 2014;87(9):12-13. |
R835433 (2014) R835433 (Final) |
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Uyghurturk D, Goin D, Martinez-MierEA, Woodruff T, DenBesten P. Maternal and fetal exposures to fluoride during mid-gestation among pregnant women in northern California. ENVIRONMENTAL HEALTH 2020;19(1):38. |
R835433 (Final) |
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Vandenberg LN, Ågerstrand M, Beronius A, Beausoleil C, Bergman A, Bero LA, Bornehag CG, Boyer CS, Cooper GS, Cotgreave I, Gee D, Grandjean P, Guyton KZ, Hass U, Heindel JJ, Jobling S, Kidd KA, Kortenkamp A, Macleod MR, Martin OV, Norinder U, Scheringer M, Thayer KA, Toppari J, Whaley P, Woodruff TJ, Ruden C. A proposed framework for the systematic review and integrated assessment (SYRINA) of endocrine disrupting chemicals. Environmental Health 2016;15(1):74. |
R835433 (2015) R835433 (Final) |
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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. Erratum to: A round robin approach to the analysis of bisphenol A (BPA) in human blood samples. Environmental Health 2016;15:43. |
R835433 (2017) R835433 (Final) |
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Varshavsky J, Zota A, Woodruff T. A Novel Method for Calculating Potency-Weighted Cumulative Phthalates Exposure with Implications for Identifying Racial/Ethnic Disparities among Reproductive-Aged Women in NHANES 2001-2012. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2016;5(19):10616-10624. |
R835433 (Final) |
Exit Exit |
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Varshavsky J, Morello-Frosch R, Woodruff T, Zota A. Dietary sources of cumulative phthalates exposure among the general population in NHANES 2005-2014. ENVIRONMENT INTERNATIONAL 2018;115:417-429. |
R835433 (Final) |
Exit Exit |
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Varshavsky J, Morello-Frosch R, Harwani S, Snider M, Petropoulou S, Park J, Petras M, Reynolda P, Nguyen T, Quach T. A Pilot Biomonitoring Study of Cumulative Phthalates Exposure among Vietnamese American Nail Salon Workers. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020;17(1). |
R835433 (Final) |
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Varshavsky J, Smith A, Wang A, Hom E, Izano M, Huang H, Padula A, Woodruff T. Heightened susceptibility:A review of how pregnancy and chemical exposures influence maternal health. Reproductive Toxicology 2020;92(SI):14-56. |
R835433 (Final) R835643 (Final) |
Exit Exit |
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Vesterinen HM, Johnson PI, Koustas E, Lam J, Sutton P, Woodruff TJ. In support of EHP's proposal to adopt the ARRIVE guidelines. Environmental Health Perspectives 2013;121(11‐12):A325. |
R835433 (2013) R835433 (2014) R835433 (Final) |
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Vesterinen HM, Morello-Frosch R, Sen S, Zeise L, Woodruff TJ. Cumulative effects of prenatal-exposure to exogenous chemicals and psychosocial stress on fetal growth: systematic-review of the human and animal evidence. PLoS One 2017;12(7):e0176331 (29 pp.). |
R835433 (2017) R835433 (Final) |
Exit Exit |
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Wang A, Padula A, Sirota M, Woodruff TJ. Environmental influences on reproductive health: the importance of chemical exposures. Fertility and Sterility 2016;106(4):905-929. |
R835433 (2016) R835433 (2017) R835433 (Final) R835643 (2016) R835643 (2017) |
Exit Exit |
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Wang A, Gerona RR, Schwartz JM, Lin T, Sirota M, Morello-Frosch R, Woodruff TJ. A suspect screening method for characterizing multiple chemical exposures among a demographically diverse population of pregnant women in San Francisco. Environmental Health Perspectives 2018;126(7):077009 (13 pp.). |
R835433 (2017) R835433 (Final) |
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Woodruff TJ, Sutton P. The Navigation Guide systematic review methodology: a rigorous and transparent method for translating environmental health science into better health outcomes. Environmental Health Perspectives 2014;122(10):1007-1014. |
R835433 (2014) R835433 (Final) |
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Zota AR, Linderholm L, Park JS, Petreas M, Guo T, Privalsky ML, Zoeller RT, Woodruff TJ. Temporal comparison of PBDEs, OH-PBDEs, PCBs, and OH-PCBs in the serum of second trimester pregnant women recruited from San Francisco General Hospital, California. Environmental Science & Technology 2013;47(20):11776-11784. |
R835433 (2017) R835433 (Final) |
Exit Exit Exit |
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Zota AR, Mitro SD, Robinson JF, Hamilton EG, Park JS, Parry E, Zoeller RT, Woodruff TJ. Polybrominated diphenyl ether (PBDEs) and hydroxylated PBDE metabolites (OH-PBDEs) in maternal and fetal tissues, and associations with fetal cytochrome P450 gene expression. Environment International 2018;112:269-278. |
R835433 (2017) R835433 (Final) |
Exit Exit Exit |
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Zota A, Mitro S, Robinson J, Hamilton E, Park J, Parry E, Zoeller R, Woodruff J. Polybrominated diphenyl ethers PBDEs and hydroxylated PBDE metabolites OH-PBDEs in maternal and fetal tissues, and associations with fetal cytochrome P450 gene expression. ENVIRONMENT INTERNATIONAL 2018;112:269-278. |
R835433 (Final) |
Exit Exit |
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Morello-Frosch R, Cushing LJ, Jesdale BM, Schwartz JM, Guo W, Guo T, Wang M, Harwani S, Syrago-Petropoulou SSE, Duong W, Park J-S, Petreas M, Gajek R, Alvaran J, She J, Dobraca D, Das R, Woodruff TJ (2016) Environmental Chemicals in an Urban Population of Pregnant Women and their Newborns from San Francisco. Environ Sci and Technol DOI:10.1021/acs.est.6b03492. |
R835433 (2016) |
Exit Exit Exit |
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Johnson PI, Sutton P, Koustas E, Vesterinen HM, Woodruff TJ. Response to correspondence by Heather Lynch, Julie Goodman and Nancy Beck Re:"Application of the Navigation Guide systematic review methodology to the evidence for developmental and reproductive toxicity of triclosan". Environ Int. 2017 Feb 21. pii:S0160-4120(17)30231-3. doi:10.1016/j.envint.2017.02.007. [Epub ahead of print] PubMed PMID:28236502. |
R835433 (2016) R835433 (Final) |
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Supplemental Keywords:
polybrominated diphenyl ether, PBDE, perfluorooctanoic acid, PFOA, placenta, trophoblast, RNA-seq, epigenomic, developmental toxicology, reproductive toxicology, perfluorinated chemicals, PFCs, environmental organic acids, EOAs, non-targeted biomonitoring, placental development, fetus, chronic psychosocial stress, prenatal health, reproductive health, birth outcomesRelevant Websites:
UCSF Program on Reproductive Health and the Environment Exit
Progress 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
- 2016 Progress Report
- 2014 Progress Report
- 2013 Progress Report
- Original Abstract
48 journal articles for this center