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

Orzabal, Marcus; Naik, Vishal D.; Lee, Jehoon; Hillhouse, Andrew; Brashear, Wesley; Threadgill, David W.; Ramadoss, Jayanth

doi:10.1016/j.trsl.2022.03.009

Cited by 9 publications

(15 citation statements)

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“…We evaluated the effects of in utero exposure to vanilla-flavored e-cig aerosols on newborn male and female mouse offspring lung transcriptomes. Lung organogenesis is a biological process highly sensitive to environmental toxicants [ 15 , 17 , 18 ], including in utero exposure to e-cig aerosols [ 10 , 22 , 23 , 28 ]. The e-cig aerosol exposure characterization results for our pregnant mice are shown in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have shown that in utero ENDS aerosol exposures can affect the developing lungs in several ways, including effects seen at the structural [ 22 ], functional [ 10 , 28 , 83 ], biochemical [ 9 , 94 ], and molecular levels [ 9 , 22 , 23 , 28 , 94 ]. While the underlying mechanisms by which in utero exposures to environmental pollutants affect the health trajectory of the lung are mainly unknown, commonly accepted explanations include epigenetic modifications and gene expression alterations in the developing fetal lung [ 82 , 95 ].…”

Section: Discussionmentioning

confidence: 99%

“…Three independent studies [ 6 , 7 , 8 ] have analyzed data collected in the Pregnancy Risk Assessment Monitoring System (PRAMS) cohorts and demonstrated that exclusive ENDS use during pregnancy can cause adverse pregnancy outcomes, including pre-term birth (adjusted prevalence ratio [PR] = 1.69; OR = 1.86), low birth weight (PR = 1.52–1.88; OR = 1.53), and infants born small for gestational age (OR = 1.76); these measures of association were all significant when compared with non-tobacco-using pregnant women [ 6 , 7 , 8 ]. Fetal growth restriction represents a clinical indicator associated with increased risk for severe complications in neonatal morbidities, including lung diseases [ 9 , 10 ]. Thus, these human data clearly show that vaping during pregnancy is associated with adverse birth effects, harming maternal and child health.…”

Section: Introductionmentioning

confidence: 99%

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Sex-Specific Alterations of the Lung Transcriptome at Birth in Mouse Offspring Prenatally Exposed to Vanilla-Flavored E-Cigarette Aerosols and Enhanced Susceptibility to Asthma

Noël

Yilmaz

Farrow

et al. 2023

IJERPH

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Currently, approximately 8 million adult Americans use electronic cigarettes (e-cigs) daily, including women of childbearing age. It is known that more than 10% of women smoke during their pregnancy, and recent surveys show that rates of maternal vaping are similar to rates of maternal cigarette smoking. However, the effects of inhaling e-cig aerosol on the health of fetuses remain unknown. The objective of the present study was to increase our understanding of the molecular effects caused by in utero exposures to e-cig aerosols on developing mouse lungs and, later in life, on the offspring’s susceptibility to developing asthma. Methods: Pregnant mice were exposed throughout gestation to either filtered air or vanilla-flavored e-cig aerosols containing 18 mg/mL of nicotine. Male and female exposed mouse offspring were sacrificed at birth, and then the lung transcriptome was evaluated. Additionally, once sub-groups of male offspring mice reached 4 weeks of age, they were challenged with house dust mites (HDMs) for 3 weeks to assess asthmatic responses. Results: The lung transcriptomic responses of the mouse offspring at birth showed that in utero vanilla-flavored e-cig aerosol exposure significantly regulated 88 genes in males (62 genes were up-regulated and 26 genes were down-regulated), and 65 genes were significantly regulated in females (17 genes were up-regulated and 48 genes were down-regulated). Gene network analyses revealed that in utero e-cig aerosol exposure affected canonical pathways associated with CD28 signaling in T helper cells, the role of NFAT in the regulation of immune responses, and phospholipase C signaling in males, whereas the dysregulated genes in the female offspring were associated with NRF2-mediated oxidative stress responses. Moreover, we found that in utero exposures to vanilla-flavored e-cig aerosol exacerbated HDM-induced asthma in 7-week-old male mouse offspring compared to respective in utero air + HDM controls. Conclusions: Overall, these data demonstrate that in utero e-cig aerosol exposure alters the developing mouse lung transcriptome at birth in a sex-specific manner and provide evidence that the inhalation of e-cig aerosols is detrimental to the respiratory health of offspring by increasing the offspring’ susceptibility to developing lung diseases later in life.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sex-Specific Alterations of the Lung Transcriptome at Birth in Mouse Offspring Prenatally Exposed to Vanilla-Flavored E-Cigarette Aerosols and Enhanced Susceptibility to Asthma

Noël

Yilmaz

Farrow

et al. 2023

IJERPH

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“…The e-cig vaping liquid (juice) was compounded with a composition of 80:20 propylene glycol (Fisher, Hampton, NH) to glycerol (Acros Organics, Fair Lawn, NJ), similar to e-cig liquids available on the market. In the present study, we selected a ratio similar to that utilized by human e-cig users to get a “throat hit” sensation, and that has a higher amount of nicotine in the vapor as documented ( Li et al, 2016 ; Ooi et al, 2019 ; Orzabal et al, 2019 , 2022 ). For the Nicotine group, animals were first acclimatized to lower doses of 5% (50 mg/mL) nicotine added in the same e-cig liquid (juice) during GD 5–8, then treated with higher doses of 10% (100 mg/mL) nicotine during GD 9–20.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2023

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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.

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“…Furthermore, changes in gene expression have been identified in zebrafish exposed to e-cigarette aerosols. These alterations in gene regulation may result in the dysregulation of genes essential for various cellular processes, thereby contributing to the observed toxic effects [ 57 , 114 , 117 , 118 , 119 , 120 ]. Lastly, e-cigarette exposure has been found to impair cellular functions and disrupt cell differentiation in Zebrafish embryos, potentially initiating cascading effects on organogenesis and tissue maturation [ 109 , 121 ].…”

Section: Cellular and Molecular Mechanisms Of E-cigarette Toxicity In...mentioning

confidence: 99%

Zebrafish (Danio rerio) as a Model for the Study of Developmental and Cardiovascular Toxicity of Electronic Cigarettes

Hussen,

Aakel,

Shaito

et al. 2023

IJMS

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The increasing popularity of electronic cigarettes (e-cigarettes) as an alternative to conventional tobacco products has raised concerns regarding their potential adverse effects. The cardiovascular system undergoes intricate processes forming the heart and blood vessels during fetal development. However, the precise impact of e-cigarette smoke and aerosols on these delicate developmental processes remains elusive. Previous studies have revealed changes in gene expression patterns, disruptions in cellular signaling pathways, and increased oxidative stress resulting from e-cigarette exposure. These findings indicate the potential for e-cigarettes to cause developmental and cardiovascular harm. This comprehensive review article discusses various aspects of electronic cigarette use, emphasizing the relevance of cardiovascular studies in Zebrafish for understanding the risks to human health. It also highlights novel experimental approaches and technologies while addressing their inherent challenges and limitations.

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

Cited by 9 publications

References 70 publications

Sex-Specific Alterations of the Lung Transcriptome at Birth in Mouse Offspring Prenatally Exposed to Vanilla-Flavored E-Cigarette Aerosols and Enhanced Susceptibility to Asthma

Sex-Specific Alterations of the Lung Transcriptome at Birth in Mouse Offspring Prenatally Exposed to Vanilla-Flavored E-Cigarette Aerosols and Enhanced Susceptibility to Asthma

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

Zebrafish (Danio rerio) as a Model for the Study of Developmental and Cardiovascular Toxicity of Electronic Cigarettes

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