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%.

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-LWJ-M)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Northeastern University
United States
Zip Code
Zhou, Wei; Meng, Xiaoxiao; Rajic, Ljiljana et al. (2018) ""Floating"" cathode for efficient H2O2 electrogeneration applied to degradation of ibuprofen as a model pollutant. Electrochem commun 96:37-41
Ashrap, Pahriya; Watkins, Deborah J; Calafat, Antonia M et al. (2018) Elevated concentrations of urinary triclocarban, phenol and paraben among pregnant women in Northern Puerto Rico: Predictors and trends. Environ Int 121:990-1002
Ferguson, Kelly K; Meeker, John D; Cantonwine, David E et al. (2018) Environmental phenol associations with ultrasound and delivery measures of fetal growth. Environ Int 112:243-250
Cathey, Amber; Ferguson, Kelly K; McElrath, Thomas F et al. (2018) Distribution and predictors of urinary polycyclic aromatic hydrocarbon metabolites in two pregnancy cohort studies. Environ Pollut 232:556-562
Lan, Jiaqi; Rahman, Sheikh Mokhlesur; Gou, Na et al. (2018) Genotoxicity Assessment of Drinking Water Disinfection Byproducts by DNA Damage and Repair Pathway Profiling Analysis. Environ Sci Technol 52:6565-6575
Wang, Poguang; Giese, Roger W (2018) Interpretation of Mass Spectral Data for the Cisplatin 1,2 Intrastrand Guanine-Guanine Adduct. Chem Res Toxicol 31:1106-1107
Hojabri, Shirin; Rajic, Ljiljana; Alshawabkeh, Akram N (2018) Transient reactive transport model for physico-chemical transformation by electrochemical reactive barriers. J Hazard Mater 358:171-177
Ferguson, Kelly K; Kamai, Elizabeth M; Cantonwine, David E et al. (2018) Associations between repeated ultrasound measures of fetal growth and biomarkers of maternal oxidative stress and inflammation in pregnancy. Am J Reprod Immunol 80:e13017
Elkin, Elana R; Harris, Sean M; Loch-Caruso, Rita (2018) Trichloroethylene metabolite S-(1,2-dichlorovinyl)-l-cysteine induces lipid peroxidation-associated apoptosis via the intrinsic and extrinsic apoptosis pathways in a first-trimester placental cell line. Toxicol Appl Pharmacol 338:30-42
Aker, Amira M; Johns, Lauren; McElrath, Thomas F et al. (2018) Associations between maternal phenol and paraben urinary biomarkers and maternal hormones during pregnancy: A repeated measures study. Environ Int 113:341-349

Showing the most recent 10 out of 163 publications