Exposure to Ambient Air Pollution and Temperature During Spermatogenesis: Impact on Men's Reproductive Health and Infertility Treatment Outcomes

精子发生过程中暴露于环境空气污染和温度：对男性生殖健康和不孕不育治疗结果的影响

• 批准号: 10617786
• 负责人: Carrie Nobles
• 金额: $ 14.77万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-04 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10617786
• 关键词: Acceleration; Accounting; Address; Aging; Air; Air Pollution; Ancillary Study; Antioxidants; Area; Behavioral; Cities; Clinical; Communities; Country; Couples; DNA Fragmentation; DNA Methylation; Data; Development; Embryonic Development; Endocrine disruption; Environmental Epidemiology; Environmental Risk Factor; Epidemiology; Epigenetic Process; Evaluation; Exposure to; Fertility; Fertilization in Vitro; Financial Hardship; Folic Acid; Foundations; Future; Grant; Health; High temperature of physical object; Household Air Pollution; Impairment; Individual; Infertility; Intervention; K-Series Research Career Programs; Link; Literature; Live Birth; Measures; Meiosis; Mentored Research Scientist Development Award; Mentors; Mentorship; Mitosis; Modeling; Observational Study; Outcome; Oxidative Stress; Oxidative Stress Induction; Ozone; Participant; Placebos; Predisposition; Pregnancy; Pregnancy Outcome; Probability; Process; Productivity; Randomized; Records; Reporting; Reproduction; Reproductive Health; Research; Risk Factors; Sampling; Seminal fluid; Site; Sodium Chloride; Spermatogenesis; Spermiogenesis; Supplementation; Temperature; Training; Treatment Side Effects; Treatment outcome; United States; Utah; Zinc supplementation; ambient air pollution; clinical translation; coarse particles; cold temperature; cost; evidence base; experience; extreme temperature; fine particles; implantation; infertility treatment; intrauterine insemination; male; male fertility; member; men; novel; offspring; pharmacologic; programs; reproductive epidemiology; reproductive outcome; sperm cell; stressor; success; systemic inflammatory response

PROJECT SUMMARY/ABSTRACT Approximately 12% of couples in the United States seek infertility treatment, which for some is associated with treatment-related side-effects, treatment-related stressors, and a significant financial burden. Although male- factor infertility contributes to an estimated 30-50% of cases of couple infertility, risk factors, mechanisms, and potential interventions for male-factor infertility have been critically understudied. Ambient air pollution and ambient temperature extremes are ubiquitous exposures associated with systemic inflammation and oxidative stress, to which the process of spermatogenesis may be uniquely susceptible. Research has found exposure to high levels of air pollution may adversely impact semen quality; however, the effect of exposure during developmentally-sensitive windows of spermatogenesis on semen quality, impacts on sperm epigenetic factors including DNA methylation, and the cumulative impact of male partner exposure on infertility treatment outcomes have been little evaluated. This study will utilize data from the Folic Acid and Zinc Supplementation Trial (FAZST) to estimate impacts of ambient environmental factors on male fertility, adding estimates of individual exposure to ambient air pollution and temperature. Adding to sparse literature from countries with low-to-moderate levels of air pollution, this study will evaluate exposure to air pollution and high and low ambient temperatures during developmentally susceptible windows of spermatogenesis (mitosis, meiosis, spermiogenesis, and spermiation) with semen quality, leveraging four repeated semen samples from more than 1,900 participants (Aim 1). Epigenetic alterations in sperm are increasingly recognized as a potential mechanism impacting male fertility, with exposure to several oxidative stress-inducing and endocrine- disrupting environmental factors linked to differential DNA methylation in sperm. This study will conduct a novel assessment of the impact of ambient air pollution exposure on sperm DNA methylation (Aim 2). Finally, this study will utilize information on outcomes of infertility treatment cycles (in vitro fertilization and intrauterine insemination cycles) and timing of treatment-related semen samples to evaluate the impact of male partner exposure to air pollution and ambient temperature during spermatogenesis on probability of pregnancy during infertility treatment, accounting for exposure windows during embryogenesis and implantation (Aim 3). This career development award will extend the candidate’s prior training and research experience in environmental and reproductive epidemiology by providing expert mentoring and targeted training in epigenetics, air quality exposure assessment, and causal inference. Her primary mentor Dr. Richard Pilsner (epigenetics), along with members of her mentoring team Dr. Timothy Canty (air quality modeling) and Dr. Laura Balzer (causal inference), with provide the needed mentoring for the candidate to establish a productive independent research program. In addition to targeted training, this K01 award will add novel evidence for the impact of ambient air pollution and temperature on men’s reproductive health and outcomes of infertility treatment.

项目概要/摘要 大约 12% 的美国夫妇寻求不孕不育治疗，对某些人来说，这与不孕不育有关 治疗相关的副作用、治疗相关的压力以及重大的经济负担。 估计 30-50% 的夫妇不孕不育病例由不孕不育因素、危险因素、机制和 对男性因素不育症的潜在干预措施尚未得到充分研究。 极端环境温度是与全身炎症和氧化相关的普遍暴露 研究发现，精子发生过程可能特别容易受到压力的影响。 严重的空气污染可能会对精液质量产生不利影响；然而， 精子发生的发育敏感窗口对精液质量的影响，对精子表观遗传因素的影响 包括 DNA 甲基化，以及男性伴侣接触对不孕症治疗的累积影响 这项研究将利用叶酸和锌补充剂的数据。 估计周围环境因素对男性生育力影响的试验（FAZST），增加了以下估计 个人暴露于环境空气污染和温度的情况增加了来自有这种情况的国家的稀疏文献。 低到中度的空气污染，本研究将评估空气污染的暴露程度以及高和低水平的空气污染 精子发生（有丝分裂、减数分裂、 精子发生和精子形成）与精液质量，利用来自更多地方的四个重复精液样本 超过 1,900 名参与者（目标 1）越来越多地认识到精子的表观遗传改变具有潜力。 影响男性生育能力的机制，暴露于几种氧化应激诱导和内分泌- 这项研究将进行一项新颖的研究，以破坏与精子中差异 DNA 甲基化相关的环境因素。 评估环境空气污染暴露对精子 DNA 甲基化的影响（目标 2）。 研究将利用有关不孕症治疗周期结果的信息（体外受精和宫内节育） 授精周期）和治疗相关精液样本的时间，以评估男性伴侣的影响 精子发生过程中暴露于空气污染和环境温度对怀孕概率的影响 不孕症治疗，考虑胚胎发生和植入期间的暴露窗口（目标 3）。 职业发展奖将扩展候选人之前在环境方面的培训和研究经验 和生殖流行病学，提供表观遗传学、空气质量方面的专家指导和有针对性的培训 她的主要导师 Richard Pilsner 博士（表观遗传学）。 她的指导团队成员 Timothy Canty 博士（空气质量建模）和 Laura Balzer 博士（因果关系） 推理），为候选人提供必要的指导，以建立富有成效的独立研究 除了有针对性的培训外，K01 奖项还将为环境空气的影响提供新的证据。 污染和温度对男性生殖健康和不孕症治疗结果的影响。