The long-term objective of our research is to reduce adverse birth outcomes such as preterm birth. Reducing preterm births to 7.6% is a Health People 2010 objective, yet preterm births continue to rise and accounted for 12.8% of live births in 2005. Unfortunately, the etiology of preterm birth, intrauterine growth restriction, and other adverse birth outcomes are poorly understood, though critical roles for infection, inflammation and oxidative stress are implicated. Limited studies relate adverse birth outcomes with exposure to Superfund-relevant toxicants. A critical knowledge gap that is identified and addressed in this proposal is the lack of information on biological explanations that link environmental pollutant exposures with preterm birth and other adverse birth outcomes. We hypothesize that Superfund-related contaminants activate reactive oxygen species-sensitive pathways in gestational tissues to promote onset of parturition and thereby increase risk for preterm birth. This hypothesis is based on the following information: 1) phthalates, trichloroethylene, and many other pollutants stimulate generation of reactive oxygen species in mammalian cells;2) reactive oxygen species can initiate apoptosis through DNA damage, non-apoptotic cell death through membrane lipid oxidation, and cytokine and prostaglandin (PG) synthesis through effects on gene transcription;3) cell death and inflammation of the placenta and gestational membranes are associated with preterm birth, intrauterine growth restriction and other adverse birth outcomes;and 4) the prostaglandins PGE2 and PGF2alpha are critical mediators of parturition. The proposed research will provide the first experimental data to support mechanisms by which environmental pollutant exposures increase women's risk for preterm birth and other adverse birth outcomes. By demonstrating that a common toxicological effect, oxidative stress, activates pathways associated with parturition, these data will provide evidence for a plausible biological explanation for environmental pollutant exposure associations with preterm birth.

Public Health Relevance

This research will identify mechanisms by which environmental contaminants activate cellular pathways involved in parturition. As such, results from this project may advance our ability to predict and prevent exposures that cause preterm birth and other adverse birth outcome, consistent with the Health People 2010 objective to reduce preterm births to 7.6%.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES017198-04
Application #
8450307
Study Section
Special Emphasis Panel (ZES1-LWJ-M)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
4
Fiscal Year
2013
Total Cost
$238,865
Indirect Cost
$3,279
Name
Northeastern University
Department
Type
DUNS #
001423631
City
Boston
State
MA
Country
United States
Zip Code
02115
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Li, Dan; Zeng, Siyu; He, Miao et al. (2016) Water Disinfection Byproducts Induce Antibiotic Resistance-Role of Environmental Pollutants in Resistance Phenomena. Environ Sci Technol 50:3193-201
Ferguson, Kelly K; Meeker, John D; Cantonwine, David E et al. (2016) Urinary phthalate metabolite and bisphenol A associations with ultrasound and delivery indices of fetal growth. Environ Int 94:531-7
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Johns, Lauren E; Ferguson, Kelly K; Meeker, John D (2016) Relationships Between Urinary Phthalate Metabolite and Bisphenol A Concentrations and Vitamin D Levels in U.S. Adults: National Health and Nutrition Examination Survey (NHANES), 2005-2010. J Clin Endocrinol Metab 101:4062-4069
Shao, Gang; MacNeil, Michael; Yao, Yuanyuan et al. (2016) Porous extraction paddle: a solid phase extraction technique for studying the urine metabolome. Rapid Commun Mass Spectrom :

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