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

Naik, Vishal D.; Lunde, Emilie R.; Ramirez, Josue; Lee, Jehoon; Ramadoss, Jayanth

doi:10.1111/acer.14250

Cited by 7 publications

(9 citation statements)

References 47 publications

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“…PA is involved in membrane phospholipid biosynthesis and is commonly used as an indicator of lipid sufficiency [33,34]. However, in the presence of alcohol (ethanol), a transphosphatidylation reaction is promoted, which then results in the production of Phosphatidylethanol (PEth) [35], an abnormal class of phospholipids that accumulates in cell membranes [36] which leads to a decrease in the bioavailability of PA. To confirm, we reported an increase in specific PEth isoforms in our rat FASD model [37] and a decrease in PA isoforms in the maternal serum [38]. We further directly added PA to excised uterine artery in vitro and demonstrated that the direct addition of PA ameliorates uterine artery (UA) dysfunction and reverses alcohol-induced decreased excitatory phosphorylation of vasodilatory eNOS [39], but it is unknown if in vivo PA can rescue end organ phenotypes in our FASD animal model.…”

Section: Introductionsupporting

confidence: 53%

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: Introductionsupporting

confidence: 53%

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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“…This has also been shown in the first trimester of pregnancy, where a positive correlation between the self‐reported number of alcohol units consumed and the PEth concentration was found (Kwak et al, 2014). PEth as a biomarker of alcohol consumption in pregnancy has been evaluated in several previous studies (Bakhireva et al, 2014; Bakhireva et al, 2017; Bracero et al, 2017; Comasco et al, 2012; Howlett et al, 2017; Kwak et al, 2012; Kwak et al, 2014; Maxwell et al, 2019; May et al, 2018; Naik et al, 2020; Yang et al, 2015). PEth was shown to have high sensitivity for recent heavy drinking, but lower sensitivity for moderate or low consumption (Kwak et al, 2014; Stewart et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Studies on PEth as a biomarker for alcohol consumption in pregnancy have mostly been carried out during late pregnancy or with newborn children (Bakhireva et al, 2014; Bakhireva et al, 2017; Bracero et al, 2017; Comasco et al, 2012; Howlett et al, 2017; Maxwell et al, 2019; May et al, 2018; Naik et al, 2020). To our knowledge, only 2 studies have investigated its use in early pregnancy (Kwak et al, 2012; Kwak et al, 2014).…”

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confidence: 99%

Phosphatidylethanol as Blood Biomarker of Alcohol Consumption in Early Pregnancy: An Observational Study in 4,067 Pregnant Women

Finanger

Spigset

Gråwe

et al. 2021

Alcoholism Clin & Exp Res

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Background: The teratogenic effects of alcohol are well documented, but there is a lack of screening methods to detect alcohol use during pregnancy. Phosphatidylethanol 16:0/18:1 (PEth) is a specific and sensitive biomarker reflecting alcohol intake up to several weeks after consumption. The aim of this study was to investigate the prevalence of positive PEth values as an indicator of early prenatal alcohol exposure in a general population of pregnant women.Methods: Rhesus typing is routinely performed in Norway in all pregnancies around gestational week 12. Rhesus-negative women have an additional test taken around week 24. Blood samples submitted to St. Olav University Hospital in Trøndelag, Norway, for Rhesus typing during the period September 2017 to October 2018 were collected. A total of 4,533 whole blood samples from 4,067 women were analyzed for PEth (limit of quantification of 0.003 µM).Results: Fifty-eight women had a positive PEth sample. Of these, 50 women were positive around gestational week 12, 3 women were positive around week 24, and in 5 cases, the timing was unknown. There were no significant differences in proportions of women with positive PEth values related to age, or rural versus urban residency.Conclusion: In an unselected pregnant population in Norway, 1.4% had a positive PEth sample around gestational week 12, whereas 0.4% had a positive sample around week 24. The use of PEth as an alcohol biomarker should be further investigated as a diagnostic tool in the antenatal setting.

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“…Some variability in the field with respect to PEth-DBS sensitivity and specificity might be explained by the differences in laboratory approach. Recent preclinical studies indicate that the homologue distribution profiles are tissue-specific ( 8 ). Another challenge is the lack of clearly established and validated cutoff concentration to constitute a ‘positive test’.…”

mentioning

confidence: 99%

Growing potential and remaining uncertainties in assessing prenatal alcohol exposure in dry blood spots

Bakhireva

2020

Pediatr Res

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

Cited by 7 publications

References 47 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

Phosphatidylethanol as Blood Biomarker of Alcohol Consumption in Early Pregnancy: An Observational Study in 4,067 Pregnant Women

Growing potential and remaining uncertainties in assessing prenatal alcohol exposure in dry blood spots

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