The Influence of Ambient Air Pollution on Fertility Using a Vitrified Donor Oocyte Bank

项目摘要/摘要 空气污染，特别是由机动车辆造成的污染，是一种无处不在的暴露，对全球健康具有重大影响 威胁，对许多不利的健康后果负有责任。新出现的证据也表明，与交通相关的 空气污染可能与试图同时怀上两胎的夫妇的生育率和生育率降低有关 而且没有医疗救助。然而，特定的污染物、暴露窗口和生物 这些关联背后的机制仍未得到充分研究。要解决这些重要的知识 ，这项建议将使用一种新的和新兴的人类受精模型-玻璃化冷冻的供体卵母细胞辅助 生殖技术(ART)-评估空气污染如何影响人类生殖 佐治亚州亚特兰大一家私人生育诊所的卵子捐赠者和卵子接受者夫妇队列(2008- 2019年)。居民暴露在与交通相关的空气污染中将在多个生物相关期间产生 在女性捐赠者、女性受者和男性受者伴侣中使用精细刻度的暴露窗口 氮氧化物、一氧化碳、细颗粒物(PM)和元素的时空模型 碳以及二氧化硫、臭氧、二氧化氮、PM10和PM成分。玻璃化冷冻供体卵母细胞 ART代表了一个理想的人群，可以研究空气与空气之间的任何联系的潜在机制 污染和生育，因为暴露在卵子和子宫环境中在时间或空间上是不相关的。 在相关的暴露窗口中，卵母细胞和精子的暴露是不相关的 受精和胚胎发育。此外，通过研究接受抗逆转录病毒治疗的患者，有可能 确定空气污染暴露的确切时间段，并直接观察早期生殖结果，例如 受精和早期胚胎发育在没有怀孕的夫妇中是永远不会被观察到的 援助。这项研究将确定卵子发生过程中空气污染暴露的独立影响。 和精子发生对受精和早期胚胎发育的独立影响，空气污染 通过卵母细胞和子宫内膜调节的妊娠结局以及空气的程度 污染会影响年轻健康女性的生育潜力。这项提案的结果将产生重大影响

PROJECT SUMMARY/ABSTRACT Air pollution, particularly due to motor vehicles, is a ubiquitous exposure and a significant global health threat, responsible for many adverse health outcomes. Emerging evidence also suggests that traffic-related air pollution may be related to lower fecundity and fertility among couples attempting to conceive both with and without medical assistance. However, the specific pollutants, exposure windows, and biological mechanisms underlying these associations remain understudied. To address these important knowledge gaps, this proposal will use a novel and emerging model of human fertility- vitrified donor oocyte assisted reproductive technology (ART)- to evaluate how air pollution influences human reproduction using a large cohort of oocyte donors and oocyte recipient couples attending a private fertility clinic in Atlanta, GA (2008- 2019). Residential exposure to traffic-related air pollution will be derived during multiple biologically relevant windows of exposure in the female donor, female recipient, and male recipient partner using fine-scale spatiotemporal models of nitrogen oxides, carbon monoxide, fine particular matter (PM), and elemental carbon as well as sulfur dioxide, ozone, nitrogen dioxide, PM10 , and PM constituents. Vitrified donor oocyte ART represents an ideal population to investigate the mechanisms underlying any associations between air pollution and fertility as exposures to the oocyte and uterine environment are uncorrelated in time or space and exposures to the oocyte and sperm are uncorrelated during the relevant exposure windows for fertilization and embryo development. Furthermore, by studying patients undergoing ART, it is possible to determine exact periods of air pollution exposure and directly observe early reproductive outcomes, such as fertilization and early embryo development that would never be observed in couples conceiving without assistance. This research will determine the independent effects of air pollution exposure during oogenesis and spermatogenesis on fertilization and early embryo development, the independent effects of air pollution on pregnancy outcomes as mediated through the oocyte and the endometrium, and the extent to which air pollution affects fertility potential in young, healthy women. Findings from this proposal will have major