PROJECT SUMMARY/ABSTRACT Exposure to air pollution in the general population is universal. Similarly, pregnancy loss is an all too common outcome affecting up to 75% of fertilized ova and 30% of recognized pregnancies. Emerging human data suggest that air pollution negatively affects early pregnancy outcomes, particularly early pregnancy loss; however the evidence is limited and the specific mechanisms and time window of susceptibility still remain to be determined. To date there are also few strategies to counteract or minimize the adverse health consequences of air pollution. Identifying potential dietary factors that could ameliorate the negative reproductive effects of air pollution would be of great public health significance as these exposures tend to be easier to directly modify than personal exposure to air pollution. Using validated spatial-temporal regression models of air pollution exposure, validated dietary questionnaires, personal air pollution monitors, and novel metabolomics biomarkers, this K99/R00 award application will determine the extent to which air pollution and its specific constituents affect fecundity, the potential for diet to modify these associations, and the possible mechanisms of action using a cohort of women undergoing in vitro fertilization in Boston, Massachusetts. Dr. Audrey Gaskins will be mentored by Dr. Francine Laden, an expert in environmental epidemiology, and Dr. Jorge Chavarro, a leader in nutrition and reproductive epidemiology. The applicant will also collaborate closely with Drs. Joel Schwartz, Brent Coull, Russ Hauser, and Chirag Patel to further her expertise in environmental epidemiology. During the K99 phase of the award, Dr. Gaskins will build on her expertise in nutritional and reproductive epidemiology and will be trained in air pollution exposure assessment using validated models to predict ambient exposure and air pollution monitors to measure continuous personal exposure. Dr. Gaskins will also receive training in the analysis of ?-omic? data in anticipation of the R00 phase where prospectively collected blood samples will be used to identify novel early effect markers of air pollution using metabolomics. Findings from the research proposed in this application may inform public health strategies to prevent early pregnancy loss, the most common adverse pregnancy outcome, while increasing our understanding of the mechanisms by which air pollution affects early pregnancy endpoints. All of this will be possible through the use of a novel study population, women undergoing in vitro fertilization where many early developmental measures can be observed and novel biomarkers can be assessed through metabolomics. The outstanding training opportunities in research areas such as air pollution and metabolomics with key leaders in the field will greatly enhance the skills and capabilities of the candidate and position her for a successful and independent career as an environmental and reproductive epidemiologist.