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.

总结