Air Particulate Pollution and Stress: Effects and Mechanisms for Long-term Maternal Obesity Risks

空气颗粒污染和压力：对孕产妇长期肥胖风险的影响和机制

• 批准号: 10673129
• 负责人: Elena Colicino
• 金额: $ 43.84万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10673129
• 关键词: Affect; Air; Air Pollution; Anthropometry; Atherosclerosis; Biological Markers; Blood; Blood Glucose; Blood Pressure; Body Weight; Body fat; Body mass index; C-reactive protein; Carotid Atherosclerotic Disease; Child; Child Health; Circulation; Cities; Data; Development; Diet; Diet Habits; Dietary Questionnaires; Early identification; Elderly; Encapsulated; Environment; Environmental Exposure; Event; Fasting; Fetus; Future; Grant; Growth; Health; High Density Lipoprotein Cholesterol; Hip region structure; Hydrocortisone; Inflammatory; Insulin Resistance; Intervention; Joints; Life; Life Cycle Stages; Life Experience; Life Stress; Link; Lipids; Longitudinal Studies; Measures; Mediator; Mental Depression; Metabolic; Metabolism; Mexico; MicroRNAs; Mothers; Obesity; Organ; Orosomucoid; Outcome; Particulate; Pathway interactions; Pattern; Physiological; Placenta; Plasma; Pollution; Postpartum Period; Predisposition; Pregnancy; Pregnancy Trimesters; Process; Psychosocial Stress; Public Health; RNA; Research; Resources; Risk Factors; Role; Salivary; Sampling; Second Pregnancy Trimester; Signal Transduction; Stress; Testing; Time; Tissues; Triglycerides; Violence; Weight; Weight Gain; Woman; Women' s Health; Work; adipokines; air filter; cardiometabolism; carotid intima-media thickness; causal model; child bearing; cost; experience; extracellular vesicles; fetal programming; fine particles; follow-up; high risk population; hypothalamic-pituitary-adrenal axis; indoor air; inflammatory marker; maternal obesity; maternal outcome; maternal weight; metabolome; metabolomics; microRNA biomarkers; nanosized; obesity risk; particle; post pregnancy; prevent; programs; recruit; social stressor; stress reduction; trophoblast; ultrasound; vesicular release

SUMMARY In pregnancy, women typically gain 16-40 pounds and undergo numerous physiological changes with potentially long-lasting consequences. Yet, research on pregnancy as a window of susceptibility to environmental exposures has focused primarily on the child and largely overlooked women’s long-term weight gain and cardiometabolic health. Emerging risk factors for obesity include air pollution that acts via respirable fine particles <2.5 μm (PM2.5) and psychosocial stress. Our preliminary data identify pregnancy as a unique window of vulnerability to PM2.5 and stress for women, indicating that effects of air pollution and stress during pregnancy may be critical for women’s health over their lifecourse. Pregnancy requires the development of a new organ— the placenta—which has long been recognized as a mediator of fetal programming. Increasing evidence implicates micro (mi)RNAs as regulators of this process, but their role in long-term maternal programming has not been considered. Supported by previous work and our preliminary data, we hypothesize that exposures during pregnancy disrupt miRNA signals released by placental trophoblasts within nano-sized extracellular vesicles (EVs) into the maternal circulation, programming maternal tissues toward obesity and cardiometabolic conditions. To our knowledge, the joint effects of air pollution and stress on mothers during pregnancy have not been studied, nor have EV-miRNAs been investigated as potential long-term, pregnancy-specific mechanisms regulating maternal outcomes. We will address these gaps in the PROGRESS study, a high-risk population in Mexico City with high but variable PM2.5 exposure and high psychosocial stress exposure. By studying PROGRESS mothers recruited in pregnancy, we can cost-effectively conduct a longitudinal study from the 2nd trimester through 10 years after pregnancy. We will also conduct state-of-the-art plasma metabolomic profiling to enhance capacity of identifying early metabolic changes. In Aim 1, we will determine the impact of higher PM2.5 exposure during pregnancy on weight retention 1 year post-partum, as well as on adiposity (weight, BMI, waist/hip circumferences, body fat %), cardiometabolic biomarkers (blood glucose, insulin resistance, lipids, adipokines) and ultrasound-based measures of subclinical carotid atherosclerosis longitudinally over 10 years. In Aim 2, we will determine the impact of higher levels of stress from life experiences (violence, depression, negative life events) and stress biomarkers (diurnal salivary cortisol rhythms) during pregnancy on those same adiposity and cardiometabolic endpoints—independently and/or jointly with higher PM2.5 exposure during pregnancy. In Aim 3, we will investigate the impact of PM2.5 and stress on placenta-specific EV-miRNA during pregnancy and on the women’s metabolome 1 month and 4 years after delivery. In Aim 4, we will apply statistical causal modeling to characterize the patterns linking EV-miRNA and metabolomics with PM2.5, stress, cortisol rhythms, and maternal adiposity and cardiometabolic health. If successful, our work will impel interventions that may help millions of women to prevent lifelong changes in body weight and adverse cardiometabolic outcomes.

概括 在怀孕中，妇女通常会增加16-40磅，并经历许多身体变化 长期后果。然而，关于怀孕的研究是对环境敏感的窗口 暴露主要集中在孩子上，并在很大程度上忽略了妇女的长期体重增加和 心脏代谢健康。肥胖的新兴危险因素包括空气污染，通过可呼吸的细颗粒起作用 <2.5μm（PM2.5）和社会心理压力。我们的初步数据将怀孕确定为独特的窗口 妇女对PM2.5的脆弱性和压力，表明空气污染和怀孕期间的压力影响 对于妇女的生命可能至关重要。怀孕需要开发新器官 - 长期以来一直被认为是胎儿编程的调解人的餐桌。越来越多的证据 暗示微（MI）RNA作为此过程的监管机构，但它们在长期母体编程中的作用已有 不考虑。在先前的工作和我们的初步数据的支持下，我们假设暴露 在怀孕期间破坏miRNA信号由纳米大小细胞内胎盘滋养细胞释放 蔬菜（EV）进入母体循环，编程肥胖和心脏代谢的遗产组织 状况。据我们所知，空气污染和压力对怀孕期间母亲的关节影响尚未 被研究了，也没有研究EV-MIRNA作为潜在的长期，妊娠特异性机制 调节母校的结果。我们将在进度研究中解决这些差距，这是高风险人群 墨西哥城具有较高但可变的PM2.5暴露和高的社会心理压力暴露。通过学习 在怀孕中招募的进步母亲，我们可以从2nd进行成本效率进行纵向研究 怀孕10年后的三个月。我们还将进行最先进的血浆代谢组分析 增强识别早期代谢变化的能力。在AIM 1中，我们将确定更高的影响 PM2.5怀孕期间的体重减轻后1年，以及肥胖（重量，BMI， 腰围/臀部圆，体内脂肪％），心脏代谢生物标志物（血糖，胰岛素抵抗，脂质，脂质， 脂肪因子）和基于超声的亚临床颈动脉粥样硬化措施在10年内纵向。 在AIM 2中，我们将确定生活经历较高压力的影响（暴力，抑郁， 妊娠期间的负面寿命事件）和压力生物标志物（昼夜唾液皮质醇节奏） 肥胖和心脏代谢终点 - 独立地和/或共同的PM2.5在较高的情况下暴露于期间 怀孕。在AIM 3中，我们将研究PM2.5和压力对Pleceta特异性EV-MIRNA的影响 怀孕和妇女代谢组1个月零4年。在AIM 4中，我们将应用统计数据 因果建模以表征将EV-MIRNA和代谢组学与PM2.5，压力，皮质醇联系起来的模式 节奏，产妇肥胖和心脏代谢健康。如果成功，我们的工作将促进干预措施 可能有助于数百万妇女防止体重和不良心脏代谢结果的终生变化。