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

项目总结/摘要 空气污染，特别是机动车造成的空气污染，是一种无处不在的暴露，也是一种严重的全球健康问题。 威胁，负责许多不利的健康结果。新出现的证据还表明， 空气污染可能与试图同时怀孕的夫妇的生育力和生育力降低有关。 而且没有医疗救助然而，具体的污染物，暴露窗口，和生物 这些关联的机制仍然没有得到充分研究。为了解决这些重要的知识 gaps，这项提案将使用一种新的和新兴的人类生育模式-玻璃化供体卵母细胞辅助 生殖技术（ART）-评估空气污染如何影响人类生殖，使用大型 在佐治亚州亚特兰大的一家私人生育诊所就诊的卵母细胞供体和卵母细胞受体夫妇队列（2008- 2019年）。住宅暴露于交通相关的空气污染将在多个生物相关的 女性供体、女性受体和男性受体伴侣的暴露窗口（使用精细量表） 氮氧化物、一氧化碳、细颗粒物和元素的时空模型 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，以研究空气与人类之间任何联系的潜在机制。 污染和生育力，因为暴露于卵母细胞和子宫环境在时间或空间上是不相关的 在相关的暴露窗口期间，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ART的患者， 确定空气污染暴露的确切时期，并直接观察早期生殖结果，例如 受精和早期胚胎发育，这在没有怀孕的夫妇中是永远不会观察到的。 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影响， 通过卵母细胞和子宫内膜介导的妊娠结局，以及空气 污染影响年轻健康妇女的生育潜力。这项提案的结果将具有重大意义。

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