E-cigarette exposure during pregnancy impairs uterine artery blood flow and feto-placental function

The popularity of electronic cigarettes (e-cigs) has risen in recent years, largely due to perceptions of reduced harm compared with traditional tobacco cigarettes. E-cig use has spread into vulnerable populations such as adolescents and individuals of reproductive age, yet their safety during pregnancy remains poorly understood. E-cigs differ from conventional cigarettes in composition, and their aerosolized components may uniquely affect the uterine environment and placental function. Proper placental development, maternal vascular remodeling, and tone are essential for healthy pregnancy outcomes, but it remains unclear how e-cig aerosol components affect these processes. To address this gap, we investigated how in utero exposure to sub-ohm e-cig aerosols, with and without nicotine, affects maternal and fetal cardiovascular function, uterine vascular function, and placental morphology. Pregnant female FVB/J mice were exposed to filtered air, vehicle (propylene glycol/vegetable glycerin; PG:VG or PV), or vehicle with nicotine (PV + Nicotine) from embryonic day (E) 0.5 to E17.5 (4 h/day, 5 days/week). Maternal and fetal cardiovascular parameters were assessed at E16.5 via echocardiography and ultrasound. At E17.5, maternal, fetal, and placental tissues were collected for histological and molecular analysis. E-cig exposure resulted in maternal diastolic dysfunction, reduced uterine artery blood flow, fetal bradycardia, structural alterations in the placenta, and reduced placental sufficiency. These effects were observed in both e-cig exposure groups, with some differences between the PV and PV + Nicotine groups, suggesting that exposure to aerosolized e-cig vehicle components alone can also contribute to gestational impairments. Our findings demonstrate that e-cig exposure during pregnancy disrupts cardiovascular adaptation and fetal development, highlighting the need for reevaluation of e-cig safety during pregnancy and guiding future mechanistic studies of its effects on placental and vascular dysfunction.