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Background <p>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.</p> Methods <p>We exposed adult pregnant C57BL/6J female mice to flavored e-cigarettes with and without nicotine (VAPE NIC &amp; VAPE). We measured implantation success (<i>N</i> = 10 SHAM, <i>N</i> = 17 VAPE, <i>N</i> = 13 VAPE NIC), erythrocyte presence (<i>N</i> = 29 SHAM, <i>N</i> = 29 VAPE, <i>N</i> = 26 VAPE NIC) and embryo elongation (<i>N</i> = 25 SHAM, <i>N</i> = 29 VAPE, <i>N</i> = 22 VAPE NIC) per implant site at day 6.5 at 13-21 weeks of age. Fetal and placental weight (<i>N</i> = 11 SHAM, <i>N</i> = 14 VAPE, <i>N</i> = 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 (<i>N</i> = 7 total, <i>N</i> = 3 sex-specific).</p> Results <p>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 (<i>Hif1a</i>), prostaglandin-endoperoxide synthase 2 (<i>Ptgs2</i>), glutathione peroxidase family members 2 and 3 (<i>Gpx2</i>/<i>Gpx3</i>), thioredoxin reductase 1 (<i>Txnrd1</i>), and mitogen-activated protein kinase 1 (<i>Mapk1</i>) exhibit marked decreases in placental tissue depending on fetal sex and nicotine presence.</p> Conclusions <p>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.</p>

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Flavored e-cigarettes modulate embryo development, fetal growth, and potentiate early fetal demise without nicotine

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月28日

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  • Margeaux W. Marbrey,
  • Samuel M. Cripps,
  • Rennica Huang,
  • Bryan M. Kistner,
  • Aanvi Somany,
  • Elizabeth S. Douglas,
  • Kathleen M. Caron

摘要

Background

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.

Methods

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).

Results

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.

Conclusions

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.