Investigating the Effects of Prenatal E-cigarette Exposure on Postnatal Liver Histology

The electronic cigarette (e-cigarette) entered the American market in the mid-2000s and quickly became popular. This product poses a significant threat to youth with 1.63 million students reporting use in 2024. Adverse health effects to different organs are well known. The liver is less studied, and despite its role in detoxification of e-cigarette chemicals, is a target of injury. Unlike the known effects of cigarettes and nicotine on the liver from adult or prenatal exposure, effects of prenatal exposure to e-cigarettes on liver remain to be defined. The current study investigated the effects of prenatal exposure of e-cigarettes on liver histology. Female mice aged 8-12 weeks were exposed to e-cigarette (Vuse Alto Golden Tobacco, 5% nicotine) aerosol for 1h daily, with a 2sec puff, 2x/min. Sham mice were exposed to air. Exposure began 4 days before introduction to males for mating and ended with pup birth. Pups were weaned and fasted at 21-24 days old and sacrificed for liver collection. Liver sections were stained with hematoxylin & eosin for microscopic analysis and scoring for the following criteria: Lipid droplets, cellularity/interstitial cellularity/inflammatory cell infiltration, extracellular matrix, perivascular cellularity around triads. Scores represented number of foci for each criterion in each visual filed and ranged from 0 to 4, with a core of 4 ≥4 foci. Statistical analysis was performed with two-way ANOVA. Exposure to e-cigarette aerosol did not cause differences in any of the criteria analyzed in liver sections from male and female mice. However, the cellularity/interstitial cellularity/inflammatory cell infiltration criteria trended towards higher (P=0.052) in female mice. Liver sections from a male and female from the same litter exposed to the aerosol presented abnormal cellularity in several foci. Results show that no microscopic changes to the liver are indicated at 21-24 days postnatal. Since histologic changes in response to toxic stimuli can take longer to appear, future studies should analyze cellular and molecular pathways which may be dysregulated by prenatal exposure, as well as determine whether prenatal exposure increases susceptibility to other liver toxins later in life.