Uteroplacental Vasculature and Fetal Growth after Plastic Particle Exposure

PROJECT SUMMARY/ABSTRACT In humans, fetal growth restriction (FGR) and impaired placental development are associated with infant morbidity and mortality and susceptibility to adulthood diseases. In pregnant animals, inhalation of particles alters the functionality of the uteroplacental vasculature, leading to impaired placental and fetal growth. Particulate matter (PM) can target the uteroplacental vasculature in multiple ways. One way by which particles can disrupt the uteroplacental vasculature is by impairing vasodilation. During pregnancy, uterine vessels must be sensitive to vasodilation mediators to meet the dynamic needs of the placenta and fetus. Central to this vasoreactivity is the endothelial cell that translates signals from the blood to the vascular smooth muscle cells, leading to vessel dilation or constriction. Additionally, the placenta is a critical organ for the diffusion of oxygen and transport of nutrients to the developing fetus. PM can impair development of the placental vasculature that allows for maternal-fetal exchange and decrease the ratio of placental-to-fetal tissue, known as placental efficiency. Our laboratory recently showed that plastic particles can translocate through the placenta to the fetus after pulmonary exposure, suggesting that the particles directly interact with the uteroplacental vasculature. The environmental burden of plastics is exponentially increasing. Micro’ nanoplastics (MNPs) represent a ubiquitous exposure concern for the general population and for vulnerable groups, such as pregnant women, it is important to elucidate how MNP inhalation may affect fetal development. These particles are generated and suspended in the air by the combustion of bulk plastic or through slower processes like mechanical degradation where a bulk plastic fragments into small pieces in the microparticle (>100 nm) and nanoparticle (<100 nm) size range. Our preliminary data demonstrates that MNP inhalation in virgin female rats disrupts uterine vascular reactivity. Furthermore, using a pregnancy model of MNP inhalation throughout gestation, we observed FGR, increased placental weight, and decreased placental efficiency suggesting the placenta is a target organ of MNPs in rats. Therefore, the central hypothesis of this proposal is that maternal inhalation of MNP throughout gestation decreases placental efficiency by impairing uterine vasodilation and disrupting development of the placental vasculature in rats. The aims in this proposal will investigate the mechanisms by which repeated maternal MNP inhalation dysregulates the uterine vasculature and placental development, thus contributing to FGR. Aim 1 will identify mechanisms of impaired uterine vascular reactivity and how endothelial cell function is altered after maternal MNP exposure. Aim 2 will determine how maternal MNP inhalation modifies development of the placental vasculature using histopathological analyses and immunohistochemistry. This research will identify mechanisms of MNP induced FGR and present potential targets for therapeutic intervention. By completing the proposed research, courses, and training the Principal Investigator will be trained independently conduct state- of-the-art experimental techniques and carry out cardiovascular and reproductive toxicological research.