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.

项目总结/文摘