PROJECT SUMMARY/ABSTRACT Air pollution, particularly due to motor vehicles, is a ubiquitous exposure and a significant global health threat, responsible for many adverse health outcomes. Emerging evidence also suggests that traffic-related air pollution may be related to lower fecundity and fertility among couples attempting to conceive both with and without medical assistance. However, the specific pollutants, exposure windows, and biological mechanisms underlying these associations remain understudied. To address these important knowledge gaps, this proposal will use a novel and emerging model of human fertility- vitrified donor oocyte assisted reproductive technology (ART)- to evaluate how air pollution influences human reproduction using a large cohort of oocyte donors and oocyte recipient couples attending a private fertility clinic in Atlanta, GA (2008- 2019). Residential exposure to traffic-related air pollution will be derived during multiple biologically relevant windows of exposure in the female donor, female recipient, and male recipient partner using fine-scale spatiotemporal models of nitrogen oxides, carbon monoxide, fine particular matter (PM), and elemental carbon as well as sulfur dioxide, ozone, nitrogen dioxide, PM10 , and PM constituents. Vitrified donor oocyte ART represents an ideal population to investigate the mechanisms underlying any associations between air pollution and fertility as exposures to the oocyte and uterine environment are uncorrelated in time or space and exposures to the oocyte and sperm are uncorrelated during the relevant exposure windows for fertilization and embryo development. Furthermore, by studying patients undergoing ART, it is possible to determine exact periods of air pollution exposure and directly observe early reproductive outcomes, such as fertilization and early embryo development that would never be observed in couples conceiving without assistance. This research will determine the independent effects of air pollution exposure during oogenesis and spermatogenesis on fertilization and early embryo development, the independent effects of air pollution on pregnancy outcomes as mediated through the oocyte and the endometrium, and the extent to which air pollution affects fertility potential in young, healthy women. Findings from this proposal will have major