Influence of Dietary Lipids on Gestational Outcomes of Ozone Exposure

膳食脂质对臭氧暴露妊娠结局的影响

• 批准号: 10752615
• 负责人: Russell Hunter
• 金额: $ 4.12万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-05 至 2024-08-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10752615
• 关键词: Acute; Age; Air; Air Pollutants; Air Pollution; Antiinflammatory Effect; Arteries; Bacteria; Biological; Blood Vessels; Bronchoalveolar Lavage Fluid; Cardiac; Cardiovascular Diseases; Cardiovascular alteration; Cardiovascular system; Cells; Chemicals; Chronic Obstructive Pulmonary Disease; Circulation; Data; Development; Diet; Dietary Fats; Dietary Fatty Acid; Dietary Supplementation; Doppler Ultrasound; Drug Metabolic Detoxication; Echocardiography; Endothelium; Environmental Exposure; Epithelium; Exposure to; Extravasation; Fatty Acids; Fetal Development; Fetus; Gases; Grant; Growth and Development function; Health; Heart Diseases; High Risk Woman; Human; Image; Incidence; Infection; Inflammation; Inflammation Mediators; Inflammatory; Inhalation; Irritants; Knowledge; Lead; Lipids; Liquid substance; Lung; Measures; Mechanics; Mediator; Modeling; Modification; Mothers; Mus; Myography; Neurodegenerative Disorders; Nutrient; Oils; Outcome; Oxygen; Ozone; Particulate Matter; Pathologic; Pathology; Physiological; Placental Insufficiency; Placentation; Pneumonia; Polyunsaturated Fatty Acids; Pre-Eclampsia; Pregnancy; Premature Birth; Pulmonary Edema; Reaction; Research; Resistance; Respiratory System; Risk; Role; Serum; Supplementation; System; Techniques; Therapeutic Intervention; Toxic effect; Training; Uterus; Vascular Diseases; Vascular remodeling; Vasoconstrictor Agents; Work; adverse pregnancy outcome; cytokine; dietary; fatty acid supplementation; fetal; heart function; hemodynamics; imaging system; immune cell infiltrate; implantation; in vivo imaging; in vivo imaging system; in vivo optical imaging; indexing; lipidomics; lung injury; metabolomics; mouse model; multidisciplinary; ozone exposure; postnatal; pregnancy hypertension; protective effect; respiratory; response; toxicant; uptake; vaping

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.

怀孕会在身体内引起广泛的生理变化，特别是 对发育中的胎儿和母亲都是脆弱的时期。子宫循环的重塑 妊娠着床期根据营养需要引起血流动力学和心血管系统的改变 胎儿的体积会扩大。胎盘植入过程中不适当的血管重组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 先兆子痫是普遍存在的血管疾病，显著增加早产的风险，如 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损伤的诱因 疾病，最近的研究表明，孕期暴露在空气污染中与 先兆子痫的发生率。目前的研究试图研究臭氧作为空气的主要成分 利用小鼠模型，污染与母体肺上皮衬里液相互作用，以及这是如何 环境暴露可能会引起全身性影响，损害正常的胎儿胎盘生长和 发展。此外，本研究旨在确定饮食中补充脂肪酸的效果。 臭氧引起的上皮衬液脂类成分改变及继发的肺损伤 曝光。饮食中的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以及可能的情况下进行了研究 对神经退行性疾病的保护作用。具体地说，欧米茄三种脂肪酸已经被证明 对呼吸道刺激物产生抗炎作用。这项研究将使用C57BL/6型号来 研究妊娠早期臭氧毒性如何导致母体系统的病理变化 血管重塑。这项建议的总体假设是，增加饮食摄取 多不饱和脂肪酸将减轻急性臭氧所致的母体肺损伤，提供保护 对血管生成重建不当引起的全身血管效应和胎盘功能不全的影响。 我们将通过对暴露于臭氧后的母体肺的脂肪组学分析来解决急性影响，以及 炎症的细胞和循环介质分析。长期的妊娠影响将是 通过超声心动图分析和体内血管渗漏成像来评估血管渗漏的程度 植入术中臭氧暴露造成的损害。这项研究完成后，这项工作将有助于 对于我们理解臭氧引起的肺损伤如何通过饮食改变的概念上的进步， 如果膳食补充剂可以被认为是一种保护措施，以保护妇女在高危的 怀孕期间暴露在空气污染中。