Placental dysfunction may have a role in various adverse pregnancy outcomes as well as in the origin of some adult diseases. However, we have limited understanding of underlying mechanisms, especially concerning the role of environmental exposures in placental pathology. Significant challenges to the field include: 1) limited knowledge of susceptibility of specific cell populations to disruption by environmental exposures; and 2) limited ability to monitor placental health during pregnancy in a safe, non-invasive manner. This project aims to use human placental villous explants as an in vitro model to address the prior challenges. To test whether oxidative stress, broadly defined as cellular oxidant challenge, is a plausible mechanism by which some toxicants elicit placental responses relevant to pregnancy outcome, we will expose placental villous explants to the model pro-oxidant tert-butyl hydroperoxide. To study susceptibility of specific cell populations, we will analyze the villi for single cell and cell type specific gene expression response to toxicant exposure. We will also characterize exosomes isolated from the culture media to determine if exosomes can inform us of placental health. Because exosomes are nano-sized vesicles secreted from living cells, including placental cells, these data could support future translational studies of the study of maternal blood plasma exosomes for monitoring placental health in a safe, relatively non-invasive manner.