Influence of Dietary Lipids on Gestational Outcomes of Ozone Exposure

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Pregnancy induces a wide range of physiological changes in the body, and can serve as a particularly vulnerable period to both the developing fetus and the mother. Remodeling of the uterine circulation during the implantation period of pregnancy results in hemodynamic and cardiovascular alterations as the nutrient needs of the fetus expand. Improper vascular reorganization during placentation can result in placental insufficiency and subsequent pathological responses to the maternal cardiac system. Gestational hypertension and preeclampsia are prevalent vascular disorders that significantly increase the risk for both premature birth as well as postnatal maternal cardiac sequelae. Air pollution is a known inducer of vascular damage and cardiac disease, and resent research has shown that gestational exposure to air pollution is correlated with increased incidence of preeclampsia. The current study seeks to examine how ozone as a major constituent of air pollution interacts with the epithelial lining fluid of the maternal lung utilizing a mouse model, and how this environmental exposure may cause systemic effects that are detrimental to normal fetoplacental growth and development. Furthermore, this study intends to determine the effect of dietary supplementation of fatty acids on modifying the lipid composition of the epithelial lining fluid, and subsequent lung injury following ozone exposure. Dietary fatty acids are important mediators of vascular integrity. Supplementation with oils high in omega three fatty acids has been studied in the context of cardiovascular integrity, as well as for possible protective effects against neurodegenerative disorders. Specifically, omega three fatty acids have been shown to produce anti-inflammatory effects against respiratory irritants. This study will use a C57BL/6 model to examine how ozone toxicity at early stages of gestation lead to systemic, pathological changes in maternal vascular remodeling. The overall hypothesis of this proposal is that increased dietary uptake of polyunsaturated fatty acids will ameliorate acute ozone induced maternal lung injury, providing a protective effect against systemic vascular effects and placental insufficiency caused by improper angiogenic remodeling. We will address the acute effects through lipidomic profiling of maternal lungs after ozone exposure, along with analysis of cellular and circulating mediators of inflammation. The long term gestational effects will be quantified through echocardiographic analysis and in vivo imaging of vascular leakage to assess the extent of damage caused by ozone exposure during implantation. Upon completion of this study, this work will contribute to the conceptual advancement of our understanding of how ozone induced lung injury can be modified by diet, and if dietary supplementation may be a considered as a protective measure for women at high risk for exposure to air pollution during pregnancy.