Impact of e-cigarette vaping aerosol exposure in pregnancy on mTOR signaling in rat fetal hippocampus.

Electronic cigarette (e-cig) use during pregnancy has become a major health concern in recent years and many view them as less harmful and may help quit or reduce combustible cigarettes. Implementing a state-of-the-art engineered vaping system, comprising an atomizer similar to those sold in vape shops, we aimed to utilize a translational e-cig inhalation delivery method to provide crucial information on the impact of prenatal e-cig aerosols on the developing brain hippocampal mTOR system in a rat model system. Gestational e-cig vaping significantly increased P-mTOR levels (p < 0.05) in the rat fetal hippocampi in the nicotine group (comprising of VG/PG + nicotine) compared to the control and the juice (comprising of VG/PG) groups. Total mTOR expression was not different among groups. Immunofluorescence imaging demonstrated P-mTOR was detected exclusively in the granule cells of the dentate gyrus of the fetal hippocampus. E-cig did not alter DEPTOR, but RAPTOR and RICTOR were higher (p < 0.05) in the Nicotine group. Gestational e-cig vaping with nicotine increased (p < 0.05) the activity and expression of 4EBP1, p70S6K, but decreased (p < 0.05) P-PKCα in the fetal hippocampi. In summary, dysregulation of mTORC1 and the related mTORC2, their activity, and downstream proteins together may play a critical role in e-cig-vaping-induced neurobiological phenotypes during development.

Impact of E-cig aerosol vaping on fetal and neonatal respiratory development and function.

Electronic cigarette (e-cig) use has increased over the past decade, and exposure to e-cig aerosols during pregnancy raises concern for maternal and fetal health. The developing fetal lung is known to be sensitive to prenatal tobacco product exposure. Utilizing a 3-pronged approach, we examined the effects of prenatal e-cig aerosols with, and without nicotine on respiratory development in a murine model. RNAseq analysis of fetal lungs revealed extensive dysregulation in gene expression. Morphologic assessment of distal airspaces in neonatal lungs display an emphysematic phenotype. Respiratory mechanics of neonates display signs of increased respiratory workload, with increased resistance and decreased compliance. These data are novel and provide evidence that prenatal e-cig exposure may result in altered lung function or development of disease.

Impact of gestational electronic cigarette vaping on amino acid signature profile in the pregnant mother and the fetus.

BACKGROUND: Electronic cigarettes (e-cigs) are a form of tobacco product that has become increasingly popular over the past decade. Despite the known health consequences of tobacco product exposure during pregnancy, a substantial number of daily smokers will continue to smoke during pregnancy. Our current knowledge on the effects of e-cig aerosol exposure during pregnancy is limited to a small number of animal studies, which have identified several e-cig aerosol-induced disruptions to the physiology of normal development. METHODS: To further assess the impact of prenatal e-cig aerosol exposure on maternal and fetal health, we examined the amino acid signature profiles in maternal and fetal plasma, as well as in the fetal lungs, a sensitive target organ for prenatal tobacco product exposure. Pregnant Sprague Dawley rats were randomly assigned to one of three groups and were exposed to either e-cig aerosols containing nicotine, e-cig aerosols without nicotine, or room air. Dams were exposed utilizing a state-of-the-art custom engineered e-cig vaping system that is compatible with commercially available e-cig atomizers and enables a translational inhalation delivery method comparable to human vaping. RESULTS: We determined that gestational exposure to e-cig aerosols results in significant alterations to the amino acid profile in the maternal and fetal compartments, including the fetal lungs. The data shows a targeted disruption to the nitric oxide pathway, branched-chain amino acid metabolism, fetal protein synthesis, and urea cycle. CONCLUSION: The data presented herein provides additional support that gestational e-cig aerosol exposure can impact crucial biological processes and exemplifies the need for extensive research on exposure to e-cig aerosols.

Gestational binge alcohol-induced alterations in maternal uterine artery transcriptome.

Binge alcohol exposure during pregnancy results in diminished vessel function and altered proteome in the maternal uterine artery. We aimed to utilize high throughput RNA-seq deep-sequencing to characterize specific effects of binge alcohol exposure during pregnancy on the uterine artery transcriptome, and gain insight into mechanisms underlying alcohol-mediated uterine artery dysfunction. Pregnant Sprague-Dawley rats assigned to Pair-Fed Control or Alcohol groups, received a once-daily orogastric gavage in a binge paradigm. RNA-sequencing using Illumina NextSeq 500, identified 13,941 genes; 40 significantly altered genes were altered by log2(fold change) > 2; 27 genes were upregulated and 13 were downregulated in the Alcohol group. Transcripts altered included those which encode for aldehyde dehydrogenases, matrix metalloproteases, and molecules vital for vasodilation and vascular remodeling. Biological pathways that were disproportionally altered by alcohol were proline and citrulline biosynthesis/metabolism. Disruption of these pathways suggests candidate mechanism(s) for alcohol-mediated impairments to the proteome and vascular function.

Chronic exposure to e-cig aerosols during early development causes vascular dysfunction and offspring growth deficits.

Increasing popularity of electronic cigarettes (e-cigs), including among women of reproductive age, is attributed to its perceived safety compared to conventional tobacco. However, there is a major knowledge gap surrounding the effects of e-cig aerosols on pregnancy and fetal development. We aimed to evaluate the effects of vaping e-cigs during gestation on offspring growth and to asses if growth deficits are accompanied by altered maternal and fetal vascular hemodynamics. Sprague-Dawley dams were assigned to Pair-Fed Control, Pair-Fed Juice, or Juice+Nicotine groups, and then underwent either a prenatal or prenatal+postnatal exposure paradigm in a custom-engineered vaping system. Mass spectrometry identified major aerosolized constituents from e-cig vaping. The Juice+Nicotine group exhibited significantly decreased fetal weight and crown-rump length (↓46.56%, and ↓23.83%, respectively). Pre- and postnatal exposure to Juice+Nicotine resulted in decreased pup weight at postnatal day (PND) 4-10. Crown-rump length was decreased by 24.71% on PND 10. Blood flow in the Juice+Nicotine group was decreased in the maternal uterine and fetal umbilical circuits by 49.50% and 65.33%, respectively. We conclude that chronic exposure to e-cig aerosols containing nicotine during early development can have deleterious health effects on the exposed offspring. Vaping e-cigs containing nicotine during pregnancy lead to a reduction in offspring weight and crown-rump length, associated with a marked decrease in blood flow in both the maternal uterine and fetal umbilical circulation (a strong indicator of growth restriction). Thus, chronic exposure to e-cig aerosols containing nicotine can lead to potentially harmful developmental effects in early life.