PDF(Pubmed)
Abstract：
Studies have shown cerebrovascular dysfunction in offspring with full-gestational electronic cigarette (Ecig) exposure, but little is known about how individual trimester exposure impacts offspring health. This study aimed to determine if there is a critical window during gestation that contributes to vascular and anxiety-like behavioural changes seen with full-term exposure. To test this, rats were time-mated, and the pregnant dams were randomly assigned to Ecig exposure during first trimester (gestational day, GD2-7), second trimester (GD8-14), third trimester (GD15-21) or full-term gestation (GD2-21). We also assessed the effect of maternal preconception exposure. Both male and female offspring from all maternal exposure conditions were compared to offspring from dams under ambient air (control) conditions. Ecig exposure consisted of 60-puffs/day (5 days/week) using either 5 or 30 watts for each respective exposure group. We found that maternal exposure to Ecig in the second and third trimesters resulted in a decrease (23-38%) in vascular reactivity of the middle cerebral artery (MCA) reactivity in 3- and 6-month-old offspring compared to Air offspring. Further, the severity of impairment was comparable to the full-term exposure (31-46%). Offspring also displayed changes in body composition, body mass, anxiety-like behaviour and locomotor activity, indicating that Ecigs influence neurodevelopment and metabolism. Maternal preconception exposure showed no impact on offspring body mass, anxiety-like behaviour, or vascular function. Thus, the critical exposure window where Ecig affects vascular development in offspring occurs during mid- to late-gestation in pregnancy, and both 5 W and 30 W exposure produce significant vascular dysfunction compared to Air. KEY POINTS: Exposure to electronic cigarettes (Ecigs) is known to increase risk factors for cardiovascular disease in both animals and humans. Maternal Ecig use during pregnancy in rodents is found to impair the vascular health of adolescent and adult offspring, but the critical gestation window for Ecig-induced vascular impairment is not known. This study demonstrates Ecig exposure during mid- and late-gestation (i.e. second or third trimester) results in impaired endothelial cell-mediated dilatation (i.e. middle cerebral artery reactivity) and alters anxiety-like behaviour in offspring. Maternal exposure prior to conception did not impact offspring\'s vascular or anxiety-like behavioural outcomes. Rodent models have been a reliable and useful predictor of inhalation-induced harm to humans. These data indicate maternal use of Ecigs during pregnancy should not be considered safe, and begin to inform clinicians and women about potential long-term harm to their offspring.
摘要：
研究表明，全孕电子烟（Ecig）暴露后代的脑血管功能障碍，但对个体孕期暴露如何影响后代健康知之甚少。这项研究旨在确定在妊娠期间是否有一个关键窗口，这有助于在足月暴露时看到的血管和焦虑样行为变化。为了测试这个，老鼠是时间交配的，怀孕的水母在妊娠早期被随机分配到Ecig暴露(妊娠日，GD2-7),中期妊娠（GD8-14），妊娠晚期（GD15-21）或足月妊娠（GD2-21）。我们还评估了孕妇孕前暴露的影响。在环境空气（对照）条件下，将所有母体暴露条件下的雄性和雌性后代与大坝的后代进行了比较。Ecig暴露由60次抽吸/天（5天/周）组成，每个暴露组使用5或30瓦。我们发现，与Air后代相比，在妊娠中期和中期，母体暴露于Ecig会导致3个月和6个月大的后代大脑中动脉（MCA）反应性的血管反应性降低（23-38％）。Further,损伤的严重程度与足月暴露相当(31-46%).后代还显示出身体成分的变化，体重,焦虑样的行为和运动活动，表明Ecigs影响神经发育和新陈代谢。母体孕前暴露对后代体重没有影响，焦虑样的行为，或血管功能。因此，Ecig影响后代血管发育的关键暴露窗口发生在妊娠中期至晚期，与空气相比，5W和30W暴露都会产生明显的血管功能障碍。关键点：已知暴露于电子烟（Ecigs）会增加动物和人类心血管疾病的风险因素。孕妇在怀孕期间使用Ecig会损害青少年和成年后代的血管健康，但Ecig引起的血管损伤的关键妊娠窗口尚不清楚。这项研究表明，在妊娠中期和晚期（即妊娠中期或妊娠中期）暴露Ecig会导致内皮细胞介导的扩张（即大脑中动脉反应性）受损，并改变后代的焦虑样行为。受孕前母体暴露不影响后代的血管或焦虑样行为结果。啮齿动物模型已成为吸入对人类造成伤害的可靠且有用的预测指标。这些数据表明母亲在怀孕期间使用Ecigs不应被认为是安全的，并开始告知临床医生和妇女对其后代的潜在长期伤害。
