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 #
5P42ES017198-03
Application #
8375194
Study Section
Special Emphasis Panel (ZES1-LWJ-M)
Project Start
Project End
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
3
Fiscal Year
2012
Total Cost
$248,249
Indirect Cost
Name
Northeastern University
Department
Type
DUNS #
001423631
City
Boston
State
MA
Country
United States
Zip Code
02115
Ferguson, Kelly K; Colacino, Justin A; Lewis, Ryan C et al. (2017) Personal care product use among adults in NHANES: associations between urinary phthalate metabolites and phenols and use of mouthwash and sunscreen. J Expo Sci Environ Epidemiol 27:326-332
Elkin, Elana R; O'Neill, Marie S (2017) Trends in Environmental Tobacco Smoke (ETS) Exposure and Preterm Birth: Use of Smoking Bans and Direct ETS Exposure Assessments in Study Designs. Chem Res Toxicol 30:1376-1383
Ferguson, Kelly K; McElrath, Thomas F; Pace, Gerry G et al. (2017) Urinary Polycyclic Aromatic Hydrocarbon Metabolite Associations with Biomarkers of Inflammation, Angiogenesis, and Oxidative Stress in Pregnant Women. Environ Sci Technol 51:4652-4660
Park, Hae-Ryung; Harris, Sean M; Boldenow, Erica et al. (2017) Group B Streptococcus Activates Transcriptomic Pathways Related to Premature Birth in Human Extraplacental Membranes In Vitro. Biol Reprod :
Ferguson, Kelly K; Meeker, John D; Cantonwine, David E et al. (2017) Environmental phenol associations with ultrasound and delivery measures of fetal growth. Environ Int 112:243-250
Shao, Gang; Agar, Jeffrey; Giese, Roger W (2017) Cold-induced aqueous acetonitrile phase separation: A salt-free way to begin quick, easy, cheap, effective, rugged, safe. J Chromatogr A 1506:128-133
Wang, Poguang; Giese, Roger W (2017) Recommendations for quantitative analysis of small molecules by matrix-assisted laser desorption ionization mass spectrometry. J Chromatogr A 1486:35-41
Ferguson, Kelly K; Chen, Yin-Hsiu; VanderWeele, Tyler J et al. (2017) Mediation of the Relationship between Maternal Phthalate Exposure and Preterm Birth by Oxidative Stress with Repeated Measurements across Pregnancy. Environ Health Perspect 125:488-494
Aung, Max T; Johns, Lauren E; Ferguson, Kelly K et al. (2017) Thyroid hormone parameters during pregnancy in relation to urinary bisphenol A concentrations: A repeated measures study. Environ Int 104:33-40
Yuan, Ye; Meeker, John D; Ferguson, Kelly K (2017) Serum polybrominated diphenyl ether (PBDE) concentrations in relation to biomarkers of oxidative stress and inflammation: The National Health and Nutrition Examination Survey 2003-2004. Sci Total Environ 575:400-405

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