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.

怀孕会诱导体内各种生理变化，并且可以作为一个特别的生理变化 发育中的胎儿和母亲都很脆弱。子宫循环的重塑 随着营养需求，怀孕期间的植入期会导致血流动力学和心血管改变 胎儿的扩展。胎盘期间的血管重组不当会导致胎盘不足 以及随后对母体心脏系统的病理反应。妊娠高血压和 子痫前期是普遍的血管疾病，可显着增加早产的风险 以及产后产妇后遗症。空气污染是已知的血管损伤和心脏诱因 疾病，不满的研究表明，妊娠暴露于空气污染与增加有关 先兆子痫的发病率。当前的研究试图研究臭氧作为空气的主要组成部分 污染与使用小鼠模型的母体肺的上皮衬里相互作用，以及如何 环境暴露可能会导致系统性影响，这对正常的胎儿型生长有害和 发展。此外，本研究打算确定饮食补充脂肪酸的影响 修饰上皮衬里的脂质成分，然后在臭氧后随后的肺损伤 接触。饮食脂肪酸是血管完整性的重要介体。补充较高的油 在心血管完整性的背景下，已经研究了欧米茄三脂肪酸 针对神经退行性疾病的保护作用。具体而言，已经显示了欧米茄三个脂肪酸 产生针对呼吸刺激物的抗炎作用。这项研究将使用C57BL/6模型 检查妊娠初期臭氧毒性如何导致孕产妇的系统性变化 血管重塑。该提议的总体假设是增加的饮食吸收 多不饱和脂肪酸将改善急性臭氧诱发母体肺损伤，提供保护性 对全身血管效应和胎盘不足引起的胎盘重塑作用的影响。 我们将通过臭氧暴露后母体肺的脂肪组分析来解决急性影响， 分析炎症的细胞和循环介质。长期妊娠效应将是 通过超声心动图分析和血管泄漏的体内成像进行量化，以评估 植入过程中臭氧暴露造成的损害。这项研究完成后，这项工作将做出贡献 为了了解我们对臭氧诱发肺损伤的理解的概念发展，饮食可以改变 如果可以将饮食补充剂视为对高风险女性的保护措施 怀孕期间暴露于空气污染。