BACKGROUND In an effort to decrease the rates of smoking conventional tobacco cigarettes, electronic cigarettes (e-cigarettes) have been proposed as an effective smoking cessation tool. However, little is known about their toxicological impacts. This is concerning given that e-cigarette use is perceived as less harmful than conventional tobacco cigarettes during pregnancy for both the mother and fetus. OBJECTIVE The goal of this study was to test the neurodevelopmental consequences of maternal e-cigarette use on adult offspring behavior and neuroimmune outcomes. METHODS Pregnant female CD-1 mice were randomly assigned to one of three treatment groups (n=8-10 per group) and exposed daily to either filtered air, propylene glycol and vegetable glycerol (50:50 PG/VG vehicle), or to PG/VG with 16mg/mL nicotine (+Nic). Whole-body exposures were carried out for 3 h/d, 7 d/week, from gestational day (GD)0.5 until GD17.5. Adult male and female offspring (8 weeks old) were assessed across a battery of behavioral assessments followed by region-specific quantification of brain cytokines using multiplex immunoassays. RESULTS Adult offspring of both sexes exposed to +Nic exhibited elevated locomotor activity in the elevated plus maze and altered stress-coping strategies in the forced swim task. Moreover, male and female offspring exposed to PG/VG with and without nicotine had a 5.2% lower object discrimination score in the novel object recognition task. In addition to differences in offspring behavior, maternal e-cigarette exposure with nicotine led to a reduction in interleukin (IL)-4 and interferon-gamma (IFNγ) in the diencephalon, as well as lower levels of hippocampal IFNγ (females only). E-cigarette exposure without nicotine resulted in a 2-fold increase of IL-6 in the cerebellum. DISCUSSION These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.

中文翻译：

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在成年后暴露于电子烟气溶胶的小鼠成年后代中测量神经炎症和行为结果。

背景技术为了降低传统烟草香烟的吸烟率，已经提出了电子香烟（e-香烟）作为有效的戒烟工具。然而，对其毒理学影响知之甚少。考虑到在怀孕期间电子烟对母亲和胎儿的危害都小于传统烟草香烟，这令人担忧。目的本研究的目的是测试孕妇使用电子烟对成年后代行为和神经免疫结果的神经发育后果。方法将怀孕的雌性CD-1小鼠随机分为三个治疗组之一（每组8-10个），每天暴露于过滤空气，丙二醇和植物甘油（50:50 PG / VG载体）或具有16mg / mL尼古丁（+ Nic）的PG / VG。从妊娠天（GD）0.5到GD17.5，全身暴露3 h / d，7 d /周。通过一系列行为评估对成年雄性和雌性后代（8周龄）进行评估，然后使用多重免疫测定法对脑细胞因子进行区域特异性定量。结果暴露于+ Nic的两性成年后代在高架迷宫中表现出较高的运动能力，并在强迫游泳任务中改变了应激应对策略。此外，在有和没有尼古丁的情况下，暴露于PG / VG的雄性和雌性后代在新的目标识别任务中的目标识别分数均降低了5.2％。除了后代行为上的差异外，孕妇使用尼古丁暴露于电子烟中还导致二脑中白介素（IL）-4和干扰素-γ（IFNγ）的减少，以及较低水平的海马IFNγ（仅限女性）。没有尼古丁的电子烟暴露导致小脑中IL-6的2倍增加。讨论这些发现支持先前在小鼠模型中电子烟暴露对神经发育的不利发现，并为怀孕期间孕妇电子烟暴露后对成年后代的持续不良行为和神经免疫后果提供了实质性证据。https://doi.org/10.1289/EHP6067。讨论这些发现支持先前在小鼠模型中电子烟暴露对神经发育的不利发现，并为怀孕期间孕妇电子烟暴露后对成年后代的持续不良行为和神经免疫后果提供了实质性证据。https://doi.org/10.1289/EHP6067。讨论这些发现支持先前在小鼠模型中电子烟暴露对神经发育的不利发现，并为怀孕期间孕妇电子烟暴露后对成年后代的持续不良行为和神经免疫后果提供了实质性证据。https://doi.org/10.1289/EHP6067。