Consequences of Maternal Vaping on Cerebrovascular Health in Offspring

项目摘要/摘要 电子烟(E-cigs)被推广为怀孕期间吸烟的替代品， 然而，短期和长期影响仍不得而知。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非常令人担忧，因为：1) 发育中的胎儿正处于一个脆弱的时期，2)在发育过程中吸烟的程度甚至很低。 众所周知，怀孕对后代有可测量的血管健康风险。因此，有一个 迫切需要进行临床前研究，以检查与血管相关的结果，特别是在 在怀孕期间暴露的可能性。我们之前已经建立了母体蒸发在 怀孕会严重损害后代的脑血管功能(即使成年后也是如此)。 这项提案的目的是评估接触电子烟对先天出生的后代的直接影响。 其次，为了确定足月妊娠与妊娠结局之间的关系， 孕期限量暴露对大鼠脑血管结构和功能的影响 青春期和成年期的后代。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)会造成不良的妊娠环境 导致脑血管减少，后代在以后的生活中血管反应迟钝。目标1 将在已经迟钝的青少年和成年子女中直接接触电子烟 继发于宫内暴露的脑血管反应性。AIM 2将使用 母亲孕期不同的汽化暴露模式(足月妊娠与个别妊娠 曝光)以确定是否存在影响(更大)的关键曝光窗口 子代脑血管结构和功能。拟议的研究将确定 母体蒸发与子代二次直接接触的后果 生命；并确定在怀孕期间蒸发可能对 脑血管健康对后代的影响。我们预计我们的数据将提供毒理学和临床 向临床医生和消费者告知怀孕期间蒸发的后果的证据 作为监管机构在制定公共政策、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.