Consequences of Maternal Vaping on Cerebrovascular Health in Offspring

项目总结/摘要 电子烟（E-cigs）被推广为怀孕期间吸烟的替代品， 然而，其直接和长期影响仍然未知。目前的估计是5-16% 的孕妇会使用电子烟，期望电子烟的风险“降低”或“没有”。 后代健康然而，怀孕期间的吸入暴露是一个重大问题，因为： 发育中的胎儿正处于脆弱时期，2）即使是“低水平”的吸烟， 已知怀孕对后代有可测量的血管健康风险。因此，有一个 迫切需要临床前研究来检查血管相关结局，特别是在 在怀孕期间暴露。我们之前已经确定了母亲在 怀孕会严重损害后代的脑血管功能（甚至影响到成年期）。 该提案的目的是评估vape暴露对先前出生的后代的直接影响 由于母亲吸烟而导致的子宫内暴露史，其次是确定是否足月与 有限的三个月暴露会产生脑血管结构和功能的差异， 在青少年和成年生活中的后代。根据我们的初步数据，我们的总体假设是，e- 在怀孕期间使用香烟（不考虑尼古丁）会产生一个不利的妊娠环境， 导致后代在以后的生活中脑血管减少和血管反应迟钝。要求1 将联合收割机直接接触电子烟的青少年和成年子女， 继发于母体电子烟宫内暴露的脑血管反应性。目标2将使用 怀孕期间母亲vaping的不同暴露模式（足月vs个别三个月 曝光），以确定是否存在（更大程度上）影响 后代脑血管结构和功能。拟议的研究将确定 母亲vaping结合二次直接暴露于后代的后果， 生活;并确定怀孕期间的什么时间框架，vaping可能对 脑血管健康的影响我们预计我们的数据将提供毒理学和临床数据 也有证据告知临床医生和消费者怀孕期间吸烟的后果， 作为监管机构制定公共政策、指导方针或法规时的信息。

Project Summary/Abstract Electronic cigarettes (E-cigs) are promoted as an alternative to smoking during pregnancy, however the immediate and long-term effects are still unknown. Current estimates are that 5-16% of pregnant women will use e-cigs with the expectation that are either ‘reduced’ or ‘no’ risk to offspring health. Yet, inhalation exposures during pregnancy are of significant concern, because: 1) the developing fetus is at a vulnerable period, and 2) even ‘low-levels’ of smoking during pregnancy are known to have measurable vascular health risk to offspring. Thus, there is a critical need for preclinical studies to examine vascular related outcomes, particularly in the context of exposure during pregnancy. We have previously established the maternal vaping during pregnancy significantly impairs cerebral vascular function in offspring (even through adulthood). The goal of this proposal is to evaluate the direct effect of vape exposure on offspring born with prior history of in utero exposure due to maternal vaping, and secondly to determine whether full-term vs limited trimester exposure produces differences in cerebral vascular structure and function in offspring in adolescent and adult life. Based on our preliminary data, our overall hypothesis is that e- cig usage during pregnancy (irrespective of nicotine) creates a hostile gestational environment that leads to reduced cerebral vascularity and blunted vascular responses in offspring later in life. Aim 1 will combine direct e-cig exposure in adolescent- and adult-aged offspring that already have blunted cerebral vascular reactivity secondary to in utero exposure from maternal vaping. Aim 2 will use different exposure patterns of maternal vaping during pregnancy (full-term vs individual trimester exposures) to determine if there is critical exposure window that (more greatly) influences cerebral vascular structure and function in offspring. The proposed studies will identify consequences of maternal vaping combined with secondary direct exposure to offspring later in life; and identify what time frame during pregnancy that vaping might have the greatest influence on cerebral vascular health on offspring. We anticipate our data will provide toxicological and clinical evidence to inform clinicians and consumers on consequences of vaping during pregnancy, as well as information for regulatory agencies when establishing public policy, guidelines or regulations.