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September 5, 2025Open Access

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

Key Points

Flavored e-cigarettes induce embryo elongation and cause increased blood cell accumulation at implant sites, contributing to fetal demise.
Nicotine presence leads to decreased embryo to placental weight ratios, suggesting critical developmental impacts.
We measured implantation success, erythrocyte presence, and fetal weights in pregnant C57BL/6J mice to assess effects.
Findings highlight the need for caution regarding flavored e-cigarette usage during pregnancy due to potential health risks.

Abstract

Abstract 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.

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