Wetendorf Margeaux, Randall Lewis T, Lemma Mahlet T, Hurr Sophia H, Pawlak John B, Tarran Robert, Doerschuk Claire M, Caron Kathleen M
Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, North Carolina.
Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
J Endocr Soc. 2019 Sep 5;3(10):1907-1916. doi: 10.1210/js.2019-00216. eCollection 2019 Oct 1.
Electronic nicotine delivery system (e-cigarette) use is prevalent among pregnant women as a seemingly safe alternative to traditional tobacco use, known to result in fetal developmental abnormalities and impaired fertility of male offspring. However, little is known about the effects of e-cigarette use on fertility or pregnancy outcomes. A successful pregnancy is initiated by a multitude of dynamic molecular alterations in the uterus resulting in embryo implantation at day 4.5 in the mouse. We examined whether e-cigarette exposure impairs implantation and offspring health. Pregnant C57BL/6J mice were exposed five times a week to e-cigarette vapor or sham. After 4 months, e-cigarette exposed dams exhibited a significant delay in the onset of the first litter. Furthermore, exposure of new dams in early pregnancy significantly impaired embryo implantation, as evidenced by nearly complete absence of implantation sites in e-cigarette-exposed animals at day 5.5, despite exhibiting high levels of progesterone, an indicator of pregnancy. RNA microarray from day 4.5 pseudopregnant mice revealed significant changes in the integrin, chemokine, and JAK signaling pathways. Moreover, female offspring exposed to e-cigarettes exhibited a significant weight reduction at 8.5 months, whereas males exhibited a slight but nonsignificant deficiency in fertility. Thus, e-cigarette exposure in mice impairs pregnancy initiation and fetal health, suggesting that e-cigarette use by reproductive-aged women or during pregnancy should be considered with caution.
电子尼古丁传送系统（电子烟）在孕妇中很普遍，它看似是传统烟草使用的安全替代品，而已知传统烟草会导致胎儿发育异常和雄性后代生育能力受损。然而，关于使用电子烟对生育能力或妊娠结局的影响，人们知之甚少。成功的妊娠始于子宫内大量动态分子变化，最终在小鼠的第4.5天实现胚胎着床。我们研究了接触电子烟是否会损害着床和后代健康。将怀孕的C57BL/6J小鼠每周暴露于电子烟烟雾或假烟雾中五次。4个月后，接触电子烟的母鼠首次产仔的时间显著延迟。此外，在怀孕早期接触电子烟的新母鼠胚胎着床明显受损，在第5.5天，接触电子烟的动物几乎完全没有着床点，尽管其孕酮水平很高，而孕酮是妊娠的一个指标。对第4.5天假孕小鼠进行的RNA微阵列分析显示，整合素、趋化因子和JAK信号通路发生了显著变化。此外，接触电子烟的雌性后代在8.5个月时体重显著减轻，而雄性后代的生育能力则有轻微但不显著的缺陷。因此，小鼠接触电子烟会损害妊娠起始和胎儿健康，这表明育龄妇女或怀孕期间使用电子烟应谨慎考虑。
