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.

Public Health Relevance

This research will evaluate the impact of maternal exposure to air pollution on early adverse pregnancy outcomes among a unique population of women undergoing in vitro fertilization in the US where early pregnancy endpoints can be observed. Using validated spatial-temporal regression models of air pollution exposure, validated dietary questionnaires, personal air pollution monitors, and novel metabolomic biomarkers, this research 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Career Transition Award (K99)
Project #
5K99ES026648-02
Application #
9454478
Study Section
Special Emphasis Panel (ZES1)
Program Officer
Boyles, Abee
Project Start
2017-04-01
Project End
2019-03-31
Budget Start
2018-04-01
Budget End
2019-03-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Harvard University
Department
Nutrition
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
Nassan, Feiby L; Chavarro, Jorge E; Mínguez-Alarcón, Lidia et al. (2018) Residential distance to major roadways and semen quality, sperm DNA integrity, chromosomal disomy, and serum reproductive hormones among men attending a fertility clinic. Int J Hyg Environ Health 221:830-837
Mínguez-Alarcón, Lidia; Williams, Paige L; Chiu, Yu-Han et al. (2018) Secular trends in semen parameters among men attending a fertility center between 2000 and 2017: Identifying potential predictors. Environ Int 121:1297-1303
Nassan, Feiby L; Chiu, Yu-Han; Vanegas, Jose C et al. (2018) Intake of protein-rich foods in relation to outcomes of infertility treatment with assisted reproductive technologies. Am J Clin Nutr 108:1104-1112
Gaskins, Audrey J (2018) Deciphering the complex relationship between systemic inflammation and fecundity in eumenorrheic women. Fertil Steril 109:240-241
Machtinger, Ronit; Gaskins, Audrey J; Racowsky, Catherine et al. (2018) Urinary concentrations of biomarkers of phthalates and phthalate alternatives and IVF outcomes. Environ Int 111:23-31
Messerlian, Carmen; Williams, Paige L; Ford, Jennifer B et al. (2018) The Environment and Reproductive Health (EARTH) Study: A Prospective Preconception Cohort. Hum Reprod Open 2018:
Gaskins, Audrey J; Hart, Jaime E; Mínguez-Alarcón, Lidia et al. (2018) Residential proximity to major roadways and traffic in relation to outcomes of in vitro fertilization. Environ Int 115:239-246
Chiu, Y-H; Karmon, A E; Gaskins, A J et al. (2018) Serum omega-3 fatty acids and treatment outcomes among women undergoing assisted reproduction. Hum Reprod 33:156-165
Gaskins, Audrey J (2018) Recent advances in understanding the relationship between long- and short-term weight change and fertility. F1000Res 7:
Gaskins, Audrey J; Missmer, Stacey A; Rich-Edwards, Janet W et al. (2018) Demographic, lifestyle, and reproductive risk factors for ectopic pregnancy. Fertil Steril 110:1328-1337

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