Impacts of Acute Ambient Air Pollution Exposure on Women's Reproductive Health: Identifying Mechanisms and Susceptible Reproductive Processes Across the Menstrual Cycle and Early Pregnancy

急性环境空气污染暴露对女性生殖健康的影响：确定月经周期和怀孕早期的机制和易受影响的生殖过程

• 批准号: 10645818
• 负责人: Carrie Nobles
• 金额: $ 32.41万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-18 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10645818
• 关键词: 8-hydroxy-2' -deoxyguanosine; Acute; Adverse effects; Affect; Air; Air Pollution; Anti-Inflammatory Agents; Applications Grants; Aromatic Polycyclic Hydrocarbons; Aspirin; Attenuated; Binding; Biological; Biological Markers; Biological Process; Blood Platelets; Cities; Cohort Studies; Communities; Complex Mixtures; Conceptions; Couples; Data; Detection; Development; Dose; Endocrine disruption; Enrollment; Epithelium; Estradiol; Event; Exposure to; F2-Isoprostanes; Fertility; First Pregnancy Trimester; Foundations; Functional disorder; Future; Health; Household Air Pollution; Human Chorionic Gonadotropin; Individual; Infertility; Inflammation; Inflammatory; Inflammatory Response; Intervention; Ligands; Lipid Peroxidation; Live Birth; Luteal Phase; Measures; Mediating; Menstrual cycle; Menstruation; Modeling; Modification; Morbidity - disease rate; Ovulation; Oxidative Stress; Oxidative Stress Pathway; Participant; Particulate Matter; Pathway interactions; Placebos; Placentation; Platelet Activation; Policies; Policy Developments; Population; Population Study; Predisposition; Pregnancy; Pregnancy Tests; Pregnancy loss; Process; Production; Randomized; Reactive Oxygen Species; Recording of previous events; Reproduction; Reproductive Health; Reproductive Process; Research; Research Project Grants; Risk; Sampling; Seasons; Site; Sodium Chloride; Spottings; Testing; Toxic effect; Urine; Woman; Work; ambient air pollution; cell injury; cohort; design; early pregnancy; evidence base; experience; fine particles; folliculogenesis; healthy pregnancy; implantation; improved; improved outcome; novel; oxidative DNA damage; pollutant; pregnant; proliferative phase Menstrual cycle; prospective; reproductive; reproductive hormone; risk mitigation; success; systemic inflammatory response; temporal measurement; time-to-pregnancy; urinary

PROJECT SUMMARY/ABSTRACT Infertility and pregnancy loss are common and associated with significant morbidity. Ambient air pollution may affect reproductive health through alterations in the inflammatory response and increased production of reactive oxygen species, leading to cellular damage, epithelial dysfunction and platelet activation. Prior research has identified associations between air pollution exposure and population-level fertility; however, interpretation is limited by an incomplete understanding of underlying pathophysiologic processes and the reproductive windows most susceptible to air pollution exposure. This exposure misclassification risks underestimating the impacts of air pollution on women’s reproductive health and studies refining exposure windows timed to underlying biologic mechanisms remains a pressing need. This exploratory/developmental research grant proposal will leverage high-quality secondary data from a completed preconception time-to- pregnancy cohort, the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial (n=1,228), to evaluate the impact of acute exposure to ambient air pollution during susceptible windows of the menstrual cycle and in early pregnancy on women’s reproductive health and ability to achieve a live birth. We will utilize Community Multiscale Air Quality (CMAQ) models to estimate participants’ residential exposure to ambient air pollution, including the criteria pollutants, constituents of particulate matter, and polycyclic aromatic hydrocarbons. The fine spatial and temporal resolution of the air quality data will allow for assessment of acute exposure during biologically-informed windows of the menstrual cycle (preovulatory follicle development, ovulation, and implantation) and early pregnancy. Aim 1 will evaluate the impact of acute exposure to ambient air pollution and PAHs around ovulation and implantation with alterations in reproductive hormones and fecundability. Aim 2 will evaluate the impact of acute exposure to ambient air pollution and PAHs from implantation through the first trimester on risk of pregnancy loss. For both aims, we will analyze mid-cycle biospecimens in a subset of participants (n=288) to assess metabolites of exposure to polycyclic aromatic hydrocarbons and oxidative stress mechanisms, including markers of oxidative DNA damage (8-hydroxy-2’-deoxyguanosine) and lipid peroxidation (F2-isoprostanes). We will additionally leverage the unique design of the EAGeR trial to identify whether randomization to the anti-inflammatory and anti-platelet actions of low-dose aspirin mitigates the impact of air pollution exposure on women’s reproductive health. These findings will provide the foundation for future work evaluating the mechanisms through which acute exposure to ambient air pollution may impact the ability of couples and individuals to achieve a live birth, both informing policy development and identifying future intervention points to improve reproductive health.

项目总结/摘要 不孕症和流产是常见的，并与显着的发病率。环境空气污染可能 通过改变炎症反应和增加 活性氧，导致细胞损伤、上皮功能障碍和血小板活化。之前 研究已经确定了空气污染暴露与人口生育率之间的关联;然而， 由于对潜在的病理生理过程的不完全理解， 生殖窗口最容易受到空气污染的影响。这种暴露错误分类风险 低估了空气污染对妇女生殖健康的影响， 与潜在的生物机制同步的窗口仍然是一个迫切的需求。探索性/发展性 研究补助金提案将利用高质量的二级数据，从一个完整的孕前时间， 妊娠队列，阿司匹林对妊娠和生殖的影响（EAGeR）试验（n= 1，228），以评估 急性暴露于环境空气污染的影响，在月经周期的敏感窗口， 早孕对妇女生殖健康和活产能力的影响。我们将利用社区 多尺度空气质量（CMAQ）模型，以估计参与者的住宅暴露于环境空气污染， 包括标准污染物、颗粒物质成分和多环芳烃。的 空气质量数据的精细空间和时间分辨率将允许评估急性暴露， 月经周期的生物学信息窗口（排卵前卵泡发育，排卵， 胚胎植入和早孕。目标1将评价急性暴露于环境空气污染的影响 和多环芳烃在排卵和植入与生殖激素和受精能力的改变。目的 2将评估急性暴露于环境空气污染和多环芳烃的影响， 妊娠早期流产的风险。对于这两个目标，我们将分析一个子集中的中期生物标本， 参与者（n=288）评估暴露于多环芳烃和氧化 应激机制，包括氧化性DNA损伤（8-羟基-2 '-脱氧鸟苷）和脂质 过氧化（F2-异前列烷）。我们还将利用EAGeR试验的独特设计， 随机分配到低剂量阿司匹林的抗炎和抗血小板作用是否减轻了 空气污染暴露对妇女生殖健康的影响。这些发现将为 未来的工作，评估急性暴露于环境空气污染可能影响 夫妇和个人实现活产的能力，既为政策制定提供信息， 今后的干预措施将着眼于改善生殖健康。