The period of intrauterine development is a "critical window" where environmental exposures can profoundly influence the life course. Interactions between the environment and genes, whose expression is choreographed and highly influenced by the environment, significantly impact health outcomes of the developing child. Much of this interaction occurs in the placenta, a highly complex organ which serves as the site for nutrient, water, and waste exchange, immune-endocrine regulation, and environmental regulation between the mother and child. Modifications of these actions can have profound effects. For example, inappropriate downregulation of IL-10, a critical anti-inflammatory cytokine, has been related to preterm birth, and work from Project 3 in the Brown SBRP has demonstrated that exposures to PCBs in IL-10 deficient murine models leads to preterm birth. Environmental exposures, such as PCBs, have long term health consequences for intrauterine exposed children, suggesting that these exposures contribute to the phenomenon of "fetal programming". These effects are thought to be elicited molecularly as alterations to the cellular epigenome, although the precise molecular character of these epigenetic alterations has yet to be elucidated. Again, the placenta, as a regulator of fetal development, reflects these exposures, as exposures can lead to stable downregulation of specific genes, as well as to alterations to the DMA methylation status of specific genomic regions. Therefore, in this Project, we hypothesize that environmental exposure to persistent PCBs in-utero results in adverse pregnancy outcomes that are modified by genetic variation at the IL-10 gene locus, and further, that the molecular mechanism by which PCB exposures act is epigenetic and that these alterations can serve as biomarkers, defining a "molecular footprint" of intrauterine exposure captured in the placenta.
We aim to (1) examine the associations between prenatal PCB exposure, preterm birth, and fetal growth restriction;(2) assess whether functional haplotypes of the IL-10 gene promoter modify the association between PCB exposure and preterm birth or fetal growth restriction;and (3) identify a signature of gene promoter methylation alterations in human placenta as novel biomarkers of preterm birth, fetal growth restriction, and PCB exposure using genome-wide assays of DNA methylation. This will be done as part of a newly established population-based longitudinal birth cohort for Rhode Island, capturing a population of 32,000 mother-infant pairs. This unique and powerful resource provides one of the most profound environments for examining these questions.

Public Health Relevance

The over-arching goal of this Superfund Basic Research Program is to address health concerns, and to design novel remediation techniques, related to mixed exposures arising from contaminated lands and buildings, using Rhode Island as a model for appropriate research, educational, and training interventions. This projects works toward that goal by examining the health effects of environmental exposures to the population of Rhode Island.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
Application #
Study Section
Special Emphasis Panel (ZES1-LKB-D)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Brown University
United States
Zip Code
Qiu, Yang; Guo, Fei; Hurt, Robert et al. (2014) Explosive thermal reduction of graphene oxide-based materials: mechanism and safety implications. Carbon N Y 72:215-223
Shen, Rui; Suuberg, Eric M (2014) Analytical Quantification of the Subslab Volatile Organic Vapor Concentration from a Non-uniform Source. Environ Model Softw 54:1-8
Clift, Danielle; Richendrfer, Holly; Thorn, Robert J et al. (2014) High-throughput analysis of behavior in zebrafish larvae: effects of feeding. Zebrafish 11:455-61
Qin, Xiaoli; Liu, Xiaorui; Shan, Bin et al. (2014) Inhibition of eIF5A results in aberrant uterine natural killer cell function and embryo loss in mice. Am J Reprod Immunol 71:229-40
Rodd, April L; Creighton, Megan A; Vaslet, Charles A et al. (2014) Effects of surface-engineered nanoparticle-based dispersants for marine oil spills on the model organism Artemia franciscana. Environ Sci Technol 48:6419-27
Velazquez-Jimenez, Litza Halla; Hurt, Robert H; Matos, Juan et al. (2014) Zirconium-carbon hybrid sorbent for removal of fluoride from water: oxalic acid mediated Zr(IV) assembly and adsorption mechanism. Environ Sci Technol 48:1166-74
Catlin, Natasha R; Huse, Susan M; Boekelheide, Kim (2014) The stage-specific testicular germ cell apoptotic response to low-dose radiation and 2,5-hexanedione combined exposure. II: qRT-PCR array analysis reveals dose dependent adaptive alterations in the apoptotic pathway. Toxicol Pathol 42:1229-37
Catlin, Natasha R; Huse, Susan M; Boekelheide, Kim (2014) The stage-specific testicular germ cell apoptotic response to low-dose X-irradiation and 2,5-hexanedione combined exposure. I: Validation of the laser capture microdissection method for qRT-PCR array application. Toxicol Pathol 42:1221-8
Shen, Rui; Pennell, Kelly G; Suuberg, Eric M (2014) Analytical modeling of the subsurface volatile organic vapor concentration in vapor intrusion. Chemosphere 95:140-9
Sharma, Surendra (2014) Natural killer cells and regulatory T cells in early pregnancy loss. Int J Dev Biol 58:219-29

Showing the most recent 10 out of 126 publications