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: 10538297
• 负责人: Russell Hunter
• 金额: $ 4.02万
• 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/10538297
• 关键词: Acute; Address; Age; Air; Air Pollutants; Air Pollution; Antiinflammatory Effect; Arteries; Bacteria; Biological; Blood Circulation; Blood Vessels; Bronchoalveolar Lavage Fluid; Cardiac; Cardiovascular Diseases; Cardiovascular alteration; Cardiovascular system; Cells; Chemicals; Chronic Obstructive Pulmonary Disease; Data; Development; Diet; Dietary Fats; Dietary Fatty Acid; Dietary Supplementation; Doppler Ultrasound; Drug Metabolic Detoxication; Endothelium; Environmental Exposure; Epithelial; 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 of activation protein; 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; Tumor-infiltrating immune cells; Uterus; Vascular Diseases; Vascular remodeling; Vasoconstrictor Agents; Work; adverse pregnancy outcome; base; cytokine; dietary; fatty acid supplementation; fetal; heart function; hemodynamics; imaging system; 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; systemic toxicity; 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.

怀孕会引起身体一系列的生理变化，并且可以作为一种特别的生理变化。 对于发育中的胎儿和母亲来说都是脆弱期。月经期间子宫循环的重塑 妊娠着床期会因营养需求而导致血流动力学和心血管发生变化 胎儿的膨胀。胎盘形成过程中血管重组不当可能导致胎盘功能不全 以及随后对母体心脏系统的病理反应。妊娠高血压和 先兆子痫是一种常见的血管疾病，会显着增加早产的风险 以及产后产妇心脏后遗症。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，妊娠期暴露于空气污染与增加 先兆子痫的发生率。当前的研究旨在研究臭氧作为空气的主要成分如何 利用小鼠模型，污染与母体肺部的上皮衬里液相互作用，以及这是如何相互作用的 环境暴露可能会导致系统性影响，不利于胎儿胎盘的正常生长和 发展。此外，本研究旨在确定膳食补充脂肪酸的效果 改变上皮内层液体的脂质成分以及臭氧引起的随后的肺损伤 接触。膳食脂肪酸是血管完整性的重要介质。补充高含量的油 欧米伽三脂肪酸已在心血管完整性的背景下进行了研究，以及可能的作用 对神经退行性疾病的保护作用。具体来说，欧米伽三脂肪酸已被证明 对呼吸道刺激物产生抗炎作用。本研究将使用 C57BL/6 模型来 研究妊娠早期的臭氧毒性如何导致母体全身病理变化 血管重塑。该提案的总体假设是增加饮食摄入 多不饱和脂肪酸将改善急性臭氧引起的母体肺损伤，提供保护性 对抗因不当血管生成重塑引起的全身血管效应和胎盘功能不全。 我们将通过臭氧暴露后母体肺部的脂质组学分析来解决急性影响，以及 炎症细胞和循环介质的分析。长期妊娠影响将是 通过超声心动图分析和血管渗漏体内成像进行量化，以评估渗漏的程度 植入期间臭氧暴露造成的损伤。完成本研究后，这项工作将有助于 我们对如何通过饮食改变臭氧引起的肺损伤的理解的概念进步， 是否可以考虑将膳食补充剂作为高风险女性的保护措施 怀孕期间接触空气污染。