Marbrey Margeaux W, Cripps Samuel M, Huang Rennica, Kistner Bryan M, Somany Aanvi, Douglas Elizabeth S, Caron Kathleen M
Duke University School of Medicine, Department of Obstetrics & Gynecology, Division of Reproductive Sciences, 701W Main Street, Suite 510, Durham, NC, 27701, USA.
University of North Carolina Chapel Hill School of Medicine, Department of Cell Biology & Physiology, 111 Mason Farm Road, Chapel Hill, NC, 27599, USA.
Commun Med (Lond). 2025 Aug 28;5(1):373. doi: 10.1038/s43856-025-01094-0.
Electronic cigarettes (e-cigarettes) function by aerosolizing a base liquid containing nicotine and flavoring, used by an estimated 15% of pregnant women as a supposed safer alternative to traditional cigarettes. Our previous studies demonstrated e-cigarettes can delay gestation. Limited studies have examined in vivo effects on the placenta.
We exposed adult pregnant C57BL/6J female mice to flavored e-cigarettes with and without nicotine (VAPE NIC & VAPE). We measured implantation success (N = 10 SHAM, N = 17 VAPE, N = 13 VAPE NIC), erythrocyte presence (N = 29 SHAM, N = 29 VAPE, N = 26 VAPE NIC) and embryo elongation (N = 25 SHAM, N = 29 VAPE, N = 22 VAPE NIC) per implant site at day 6.5 at 13-21 weeks of age. Fetal and placental weight (N = 11 SHAM, N = 14 VAPE, N = 12 VAPE NIC) was evaluated at day 12.5 in mice aged 15-39 weeks, while placental gene expression was separately analyzed by offspring sex (N = 7 total, N = 3 sex-specific).
Here we show that e-cigarettes cause similar embryo elongation and in the absence of nicotine, exhibit elevated implant site blood cell accumulation which may contribute to fetal demise. With nicotine, e-cigarettes elicit a reduction in embryo to placental weight ratios. Genes involved in hypoxia, reactive oxygen species response, and placental growth including hypoxia inducible factor 1, alpha subunit (Hif1a), prostaglandin-endoperoxide synthase 2 (Ptgs2), glutathione peroxidase family members 2 and 3 (Gpx2/Gpx3), thioredoxin reductase 1 (Txnrd1), and mitogen-activated protein kinase 1 (Mapk1) exhibit marked decreases in placental tissue depending on fetal sex and nicotine presence.
Our findings conclude flavored e-cigarettes modulate in vivo implantation and placentation mechanisms depending on the presence of nicotine. This work presents a measure of concern for flavored e-cigarette use during pregnancy.
电子烟通过将含有尼古丁和调味剂的基础液体雾化发挥作用，据估计，15%的孕妇使用电子烟，认为其是比传统香烟更安全的替代品。我们之前的研究表明电子烟会延迟妊娠。有限的研究已考察了其对胎盘的体内影响。
我们将成年怀孕的C57BL/6J雌性小鼠暴露于含尼古丁和不含尼古丁的调味电子烟（VAPE NIC和VAPE）。在13至21周龄的第6.5天，我们测量每个植入部位的着床成功率（假手术组N = 10只，VAPE组N = 17只，VAPE NIC组N = 13只）、红细胞存在情况（假手术组N = 29只，VAPE组N = 29只，VAPE NIC组N = 26只）和胚胎伸长情况（假手术组N = 25只，VAPE组N = 29只，VAPE NIC组N = 22只）。在15至39周龄小鼠的第12.5天评估胎儿和胎盘重量（假手术组N = 11只，VAPE组N = 14只，VAPE NIC组N = 12只），同时按后代性别分别分析胎盘基因表达（共N = 7只，按性别特异性分析N = 3只）。
我们在此表明，电子烟会导致类似的胚胎伸长，且在不含尼古丁的情况下，会出现植入部位血细胞积累增加，这可能导致胎儿死亡。在有尼古丁的情况下，电子烟会使胚胎与胎盘重量比降低。涉及缺氧、活性氧反应和胎盘生长的基因，包括缺氧诱导因子1α亚基（Hif1a）、前列腺素内过氧化物合酶2（Ptgs2）、谷胱甘肽过氧化物酶家族成员2和3（Gpx2/Gpx3）、硫氧还蛋白还原酶1（Txnrd1）和丝裂原活化蛋白激酶1（Mapk1），在胎盘组织中的表达根据胎儿性别和尼古丁的存在情况显著降低。
我们的研究结果表明，调味电子烟会根据尼古丁的存在情况调节体内着床和胎盘形成机制。这项研究对孕期使用调味电子烟提出了一定的担忧。
