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

Lee, Jehoon; Orzabal, Marcus; Naik, Vishal D.; Ramadoss, Jayanth

doi:10.3389/fnins.2023.1217127

Cited by 2 publications

(1 citation statement)

References 56 publications

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“…Immunofluorescence assessments were performed using previously published protocols [46,47]. In brief, maternal uterine arteries were sectioned at 8 µm with a Leica cryostat (CM1860, Leica Biosystems, Buffalo Grove, IL, USA).…”

Section: Immunofluorescencementioning

confidence: 99%

In Vivo Administration of Phosphatidic Acid, a Direct Alcohol Target Rescues Fetal Growth Restriction and Maternal Uterine Artery Dysfunction in Rat FASD Model

Janeski,

Naik,

Carabulea

et al. 2024

Nutrients

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Fetal growth restriction is a hallmark of Fetal Alcohol Syndrome (FAS) and is accompanied by maternal uterine circulatory maladaptation. FAS is the most severe form of Fetal Alcohol Spectrum Disorder (FASD), a term for the range of conditions that can develop in a fetus when their pregnant mother consumes alcohol. Alcohol exerts specific direct effects on lipids that control fundamental developmental processes. We previously demonstrated that direct in vitro application of phosphatidic acid (PA, the simplest phospholipid and a direct target of alcohol exposure) to excised uterine arteries from alcohol-exposed rats improved vascular function, but it is unknown if PA can rescue end organ phenotypes in our FASD animal model. Pregnant Sprague-Dawley rats (n = 40 total dams) were gavaged daily from gestational day (GD) 5 to GD 19 with alcohol or maltose dextrin, with and without PA supplementation, for a total of four unique groups. To translate and assess the beneficial effects of PA, we hypothesized that in vivo administration of PA concomitant with chronic binge alcohol would reverse uterine artery dysfunction and fetal growth deficits in our FASD model. Mean fetal weights and placental efficiency were significantly lower in the binge alcohol group compared with those in the control (p < 0.05). However, these differences between the alcohol and the control groups were completely abolished by auxiliary in vivo PA administration with alcohol, indicating a reversal of the classic FAS growth restriction phenotype. Acetylcholine (ACh)-induced uterine artery relaxation was significantly impaired in the uterine arteries of chronic in vivo binge alcohol-administered rats compared to the controls (p < 0.05). Supplementation of PA in vivo throughout pregnancy reversed the alcohol-induced vasodilatory deficit; no differences were detected following in vivo PA administration between the pair-fed control and PA alcohol groups. Maximal ACh-induced vasodilation was significantly lower in the alcohol group compared to all the other treatments, including control, control PA, and alcohol PA groups (p < 0.05). When analyzing excitatory vasodilatory p1177-eNOS, alcohol-induced downregulation of p1177-eNOS was completely reversed following in vivo PA supplementation. In summary, these novel data utilize a specific alcohol target pathway (PA) to demonstrate a lipid-based preventive strategy and provide critical insights important for the development of translatable interventions.

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Section: Immunofluorescencementioning

confidence: 99%

In Vivo Administration of Phosphatidic Acid, a Direct Alcohol Target Rescues Fetal Growth Restriction and Maternal Uterine Artery Dysfunction in Rat FASD Model

Janeski,

Naik,

Carabulea

et al. 2024

Nutrients

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Influence of gestational window on offspring vascular health in rodents with in utero exposure to electronic cigarettes

Mills,

Nassabeh,

Hurley

et al. 2024

The Journal of Physiology

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Studies have shown cerebrovascular dysfunction in offspring with full‐gestational electronic cigarette (Ecig) exposure, but little is known about how individual trimester exposure impacts offspring health. This study aimed to determine if there is a critical window during gestation that contributes to vascular and anxiety‐like behavioural changes seen with full‐term exposure. To test this, rats were time‐mated, and the pregnant dams were randomly assigned to Ecig exposure during first trimester (gestational day, GD2–7), second trimester (GD8–14), third trimester (GD15–21) or full‐term gestation (GD2–21). We also assessed the effect of maternal preconception exposure. Both male and female offspring from all maternal exposure conditions were compared to offspring from dams under ambient air (control) conditions. Ecig exposure consisted of 60‐puffs/day (5 days/week) using either 5 or 30 watts for each respective exposure group. We found that maternal exposure to Ecig in the second and third trimesters resulted in a decrease (23–38%) in vascular reactivity of the middle cerebral artery (MCA) reactivity in 3‐ and 6‐month‐old offspring compared to Air offspring. Further, the severity of impairment was comparable to the full‐term exposure (31–46%). Offspring also displayed changes in body composition, body mass, anxiety‐like behaviour and locomotor activity, indicating that Ecigs influence neurodevelopment and metabolism. Maternal preconception exposure showed no impact on offspring body mass, anxiety‐like behaviour, or vascular function. Thus, the critical exposure window where Ecig affects vascular development in offspring occurs during mid‐ to late‐gestation in pregnancy, and both 5 W and 30 W exposure produce significant vascular dysfunction compared to Air. imageKey points Exposure to electronic cigarettes (Ecigs) is known to increase risk factors for cardiovascular disease in both animals and humans. Maternal Ecig use during pregnancy in rodents is found to impair the vascular health of adolescent and adult offspring, but the critical gestation window for Ecig‐induced vascular impairment is not known. This study demonstrates Ecig exposure during mid‐ and late‐gestation (i.e. second or third trimester) results in impaired endothelial cell‐mediated dilatation (i.e. middle cerebral artery reactivity) and alters anxiety‐like behaviour in offspring. Maternal exposure prior to conception did not impact offspring's vascular or anxiety‐like behavioural outcomes. Rodent models have been a reliable and useful predictor of inhalation‐induced harm to humans. These data indicate maternal use of Ecigs during pregnancy should not be considered safe, and begin to inform clinicians and women about potential long‐term harm to their offspring.

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

Cited by 2 publications

References 56 publications

In Vivo Administration of Phosphatidic Acid, a Direct Alcohol Target Rescues Fetal Growth Restriction and Maternal Uterine Artery Dysfunction in Rat FASD Model

In Vivo Administration of Phosphatidic Acid, a Direct Alcohol Target Rescues Fetal Growth Restriction and Maternal Uterine Artery Dysfunction in Rat FASD Model

Influence of gestational window on offspring vascular health in rodents with in utero exposure to electronic cigarettes

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