Influence of Dietary Lipids on Gestational Outcomes of Ozone Exposure

怀孕会引起身体的广泛生理变化，并且可以作为一种特别的 对发育中的胎儿和母亲来说都是脆弱的时期。妊娠期子宫循环的重建 妊娠着床期由于营养需求而导致血流动力学和心血管变化 胎儿会膨胀胎盘形成过程中血管重组不当可导致胎盘功能不全 以及随后对母体心脏系统的病理反应。妊娠期高血压和 先兆子痫是一种普遍的血管疾病， 以及产后母体心脏后遗症。空气污染是已知的血管损伤和心脏病的诱因。 最近的研究表明，妊娠期暴露于空气污染与增加 先兆子痫的发病率。目前的研究旨在研究臭氧作为空气的主要成分 利用小鼠模型，污染与母体肺的上皮衬里液相互作用，以及这是如何发生的。 环境暴露可引起对正常胎儿胎盘生长有害的全身效应， 发展此外，本研究旨在确定膳食补充脂肪酸的效果 改变上皮衬里液的脂质成分，以及臭氧后的肺损伤 exposure.膳食脂肪酸是血管完整性的重要介质。补充高含量的油 欧米茄3脂肪酸已经在心血管完整性的背景下进行了研究，以及可能的 对神经退行性疾病的保护作用。具体来说，欧米伽三脂肪酸已经被证明 对呼吸道刺激物产生抗炎作用。本研究将使用C57 BL/6模型， 研究如何在怀孕早期阶段臭氧毒性导致系统，病理变化，在母体 血管重塑这一建议的总体假设是， 多不饱和脂肪酸将改善急性臭氧引起的母体肺损伤， 对抗由不适当的血管生成重塑引起的全身血管效应和胎盘功能不全的作用。 我们将通过臭氧暴露后母体肺的脂质组学分析来解决急性效应，沿着 分析炎症的细胞和循环介质。长期妊娠影响将是 通过超声心动图分析和血管渗漏的体内成像进行定量，以评估 在植入过程中暴露于臭氧造成的损伤。这项研究完成后， 我们对臭氧引起的肺损伤如何通过饮食来改变的理解的概念性进展， 如果膳食补充剂可以被认为是高风险妇女的保护措施， 怀孕期间接触空气污染。

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.