PROJECT SUMMARY/ABSTRACT
Infertility and pregnancy loss are common and associated with significant morbidity. Ambient air pollution may
affect reproductive health through alterations in the inflammatory response and increased production of
reactive oxygen species, leading to cellular damage, epithelial dysfunction and platelet activation. Prior
research has identified associations between air pollution exposure and population-level fertility; however,
interpretation is limited by an incomplete understanding of underlying pathophysiologic processes and the
reproductive windows most susceptible to air pollution exposure. This exposure misclassification risks
underestimating the impacts of air pollution on women’s reproductive health and studies refining exposure
windows timed to underlying biologic mechanisms remains a pressing need. This exploratory/developmental
research grant proposal will leverage high-quality secondary data from a completed preconception time-to-
pregnancy cohort, the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial (n=1,228), to evaluate
the impact of acute exposure to ambient air pollution during susceptible windows of the menstrual cycle and in
early pregnancy on women’s reproductive health and ability to achieve a live birth. We will utilize Community
Multiscale Air Quality (CMAQ) models to estimate participants’ residential exposure to ambient air pollution,
including the criteria pollutants, constituents of particulate matter, and polycyclic aromatic hydrocarbons. The
fine spatial and temporal resolution of the air quality data will allow for assessment of acute exposure during
biologically-informed windows of the menstrual cycle (preovulatory follicle development, ovulation, and
implantation) and early pregnancy. Aim 1 will evaluate the impact of acute exposure to ambient air pollution
and PAHs around ovulation and implantation with alterations in reproductive hormones and fecundability. Aim
2 will evaluate the impact of acute exposure to ambient air pollution and PAHs from implantation through the
first trimester on risk of pregnancy loss. For both aims, we will analyze mid-cycle biospecimens in a subset of
participants (n=288) to assess metabolites of exposure to polycyclic aromatic hydrocarbons and oxidative
stress mechanisms, including markers of oxidative DNA damage (8-hydroxy-2’-deoxyguanosine) and lipid
peroxidation (F2-isoprostanes). We will additionally leverage the unique design of the EAGeR trial to identify
whether randomization to the anti-inflammatory and anti-platelet actions of low-dose aspirin mitigates the
impact of air pollution exposure on women’s reproductive health. These findings will provide the foundation for
future work evaluating the mechanisms through which acute exposure to ambient air pollution may impact the
ability of couples and individuals to achieve a live birth, both informing policy development and identifying
future intervention points to improve reproductive health.
