Mechanisms Underlying Chronic Binge Alcohol Exposure‐Induced Uterine Artery Dysfunction in Pregnant Rat

Naik, Vishal D.; Davis-Anderson, Katie; Subramanian, Kaviarasan; Lunde, Emilie R.; Nemec, Matthew; Ramadoss, Jayanth

doi:10.1111/acer.13602

Cited by 11 publications

(16 citation statements)

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“…Nutrient delivery to the fetus has been shown to be a critical factor influencing fetal growth and development (65). Substance abuse, alcohol consumption, and tobacco use during pregnancy frequently lead to IUGR as a result of poor nutrient delivery (18)(19)(20)22). Further, vaping e-cigs containing nicotine may directly inhibit acetylcholine-facilitated transport systems responsible for moving vital amino acids across the placenta (66).…”

Section: Discussionmentioning

confidence: 99%

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

Orzabal

Lunde-Young

Ramirez

et al. 2019

Translational Research

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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 leads 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.

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Section: Discussionmentioning

confidence: 99%

“…A common end-result of substance use in pregnancy is fetal growth restriction (18,19). This teratogenic effect has been well documented in studies investigating the use of alcohol and traditional cigarettes during pregnancy (20)(21)(22). Further, alcohol drinking is frequently accompanied by smoking (23,24).…”

Section: Introductionmentioning

confidence: 99%

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

Orzabal

Lunde-Young

Ramirez

et al. 2019

Translational Research

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“…This is the first study to quantify PEth levels in the maternal uterine artery, the vessel primarily responsible for delivering essential nutrients and oxygen to the developing fetus throughout pregnancy. Previous studies have demonstrated in both rat and sheep models that gestational alcohol exposure leads to uterine artery dysfunction, and that this alcoholinduced dysfunction may play an important role in FASD etiology (Gundogan et al, 2008;Naik et al, 2018;Ramadoss and Magness, 2012;Subramanian et al, 2014). Detection of all three major PEth homologues in the maternal uterine artery shows accumulation of PEth in the uterine arterial wall.…”

Section: Peth Homologues Distribution In the Maternal Primary Uterine...mentioning

confidence: 92%

“…Although few studies have examined PEth formation in maternal and fetal blood following gestational alcohol exposure (Bakhireva et al, 2014;Baldwin et al, 2015;Kwak et al, 2014), the current study is the first to examine and compare the distribution of the three major PEth homologues 16:0/18:1, 16:0/18:2, and 16:0/20:4 in both maternal and fetal blood and brain regions with well-known vulnerability to alcohol, following a chronic gestational binge exposure paradigm. Gestational alcohol exposure has been implicated in disrupting pregnancy-induced adaptations and function of the maternal uterine artery, a vessel which supplies all nutrients and oxygen essential for healthy fetal development (Gundogan et al, 2008;Naik et al, 2018;Ramadoss and Magness, 2012;Subramanian et al, 2014). Therefore, we selected the uterine artery as a tissue of interest in the maternal compartment.…”

Section: Introductionmentioning

confidence: 99%

Distribution of Phosphatidylethanol in Maternal and Fetal Compartments After Chronic Gestational Binge Alcohol Exposure

Naik

Lunde

Ramirez

et al. 2019

Alcoholism Clin & Exp Res

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Background: Phosphatidylethanol (PEth) is a promising biomarker for gestational alcohol exposure. Studies show PEth accumulation in maternal and fetal blood following alcohol exposure, however, distribution of specific PEth homologues (16:0/18:1, 16:0/18:2, 16:0/20:4) in maternal and fetal blood is unknown. Additionally, PEth levels in highly vulnerable FASD targets in maternal and fetal compartments remain unexplored. We hypothesized that all three major PEth homologues will be detectable in the maternal and fetal blood, the maternal uterine artery (a reproductive tissue that delivers oxygen and nutrients to feto-placental unit), and fetal brain regions following gestational binge alcohol exposure, and that homologue distribution profiles will be tissue-specific.Methods: Pregnant rats received once-daily oragastric gavage of alcohol (Alcohol; BAC 216 mg/ dl@4.5g/kg/day; BAC 289 mg/dl@6g/kg/day) or iso-caloric maltose-dextrin (Pair-fed control) from gestation day (GD) 5-20 or 21. Following chronic exposure, maternal and fetal tissues were analyzed for PEth homologue concentrations utilizing LC-MS/MS technology.Results: All three PEth homologues were detected in alcohol-exposed maternal blood, fetal blood, maternal uterine artery, and fetal brain regions (hippocampus, cerebral cortex, cerebellum). In both maternal and fetal blood, respectively, PEth 16:0/18:2 was more abundant compared to 16:0/18:1 (P<0.0001,~66%,↑;P=0.0159,20.4%↑) and 16:0/20:4 (P=0.0072,~25%↑;P=0.0187,19.4%↑). Maternal PEth 16:0/20:4 was ~42% higher than 16:0/18:1 (P=0.0015). Maternal PEth 16:0/18:2 and 16:0/20:4 were ~25%↑ and ~20%↑ higher than in fetal blood (P<0.05). No homologue differences were detected in the maternal uterine artery. In all fetal brain regions, PEth 16:0/18:1 was significantly higher (P<0.0001) than 16:0/18:2 (~48-78%↑) and 16:0/20:4 (~31-62%↑) concentrations. PEth 16:0/20:4 was ~18% higher than 16:0/18:1 (P<0.05) in the fetal hippocampus and cortex. Conclusion:All major PEth homologues were detected in maternal and fetal blood following chronic gestational binge alcohol exposure; homologue distribution profiles were tissue specific.

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“…The cell death is not necessarily and exclusively caused by impairments of the neurotransmitter system. Indirect effects, such as those related to the disruption of brain or uterine vasculature, may play a role in alcohol-induced cell death [ 14 , 15 , 16 ].…”

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confidence: 99%

Alcohol and the Developing Brain: Why Neurons Die and How Survivors Change

Granato

Dering

2018

IJMS

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The consequences of alcohol drinking during pregnancy are dramatic and usually referred to as fetal alcohol spectrum disorders (FASD). This condition is one of the main causes of intellectual disability in Western countries. The immature fetal brain exposed to ethanol undergoes massive neuron death. However, the same mechanisms leading to cell death can also be responsible for changes of developmental plasticity. As a consequence of such a maladaptive plasticity, the functional damage to central nervous system structures is amplified and leads to permanent sequelae. Here we review the literature dealing with experimental FASD, focusing on the alterations of the cerebral cortex. We propose that the reciprocal interaction between cell death and maladaptive plasticity represents the main pathogenetic mechanism of the alcohol-induced damage to the developing brain.

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Mechanisms Underlying Chronic Binge Alcohol Exposure‐Induced Uterine Artery Dysfunction in Pregnant Rat

Abstract: This is the first study to demonstrate maternal binge alcohol consumption during pregnancy disrupts uterine artery vascular function via impairment of the eNOS vasodilatory system.

Cited by 11 publications

References 60 publications

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

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

Distribution of Phosphatidylethanol in Maternal and Fetal Compartments After Chronic Gestational Binge Alcohol Exposure

Alcohol and the Developing Brain: Why Neurons Die and How Survivors Change

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