Assessing the Impact of Maternal Physical Activity on Small Extracellular Vesicles and Placental Vascularization During Pregnancy

Abstract

Physical activity (PA) reduces the risk for deleterious outcomes in both mother and fetus during pregnancy and improves health across the lifespan. How these benefits are bestowed remains poorly understood but may involve the placenta, the critical interface responsible for fetal growth and survival during pregnancy. This thesis first aims to determine whether small extracellular vesicles (sEVs), potential biological mediators of cell-to-cell communication, are released into circulation after acute exercise during pregnancy and how this compares in the non-pregnant state. Pregnant women were found to have greater circulating sEVs levels compared to non-pregnant controls after a moderate-intensity treadmill walk. Since exercise-associated sEVs are proposed to mediate tissue cross talk in response to exercise, exercise-associated sEVs were examined for their ability to influence trophoblasts (specialized placental cells) in vitro using the BeWo choriocarcinoma cell line. Exercise-associated sEVs from pregnant and non-pregnant women interacted with trophoblast-like cells but did not alter their proliferation, gene expression of angiogenic growth factors, or production of the pregnancy hormone, human chorionic gonadotropin. Finally, the relationship between differing intensities of maternal PA and fetoplacental vascular density in a cohort of healthy pregnant women followed prospectively from 24 weeks of gestation until term delivery. Using traditional histopathological point-counting techniques, there was no difference in the fetoplacental vascular density of individuals meeting or exceeding recommended 150 min of moderate-to-vigorous intensity PA. However, the analysis revealed unexpected associations between fetoplacental vascular density and lower intensities of PA, and sedentary time. Together, the work presented in this thesis highlight the potential for exercise-associated sEVs to communicate the benefits of PA to mother and fetus and the need to investigate the effects of varying PA intensities on placental vascular development.