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

Abstract

BACKGROUND\nPhosphatidylethanol (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.\n\n\nMETHODS\nPregnant rats received once-daily oragastric gavage of alcohol (Alcohol; BAC 216\xa0mg/[email protected]/kg/day; BAC 289\xa0mg/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.\n\n\nRESULTS\nAll 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\xa0<\xa00.0001,~66%,↑;P\xa0=\xa00.0159,20.4%↑) and 16:0/20:4 (P\xa0=\xa00.0072,~25%↑;P\xa0=\xa00.0187,19.4%↑). Maternal PEth 16:0/20:4 was\xa0~\xa042% higher than 16:0/18:1 (P\xa0=\xa00.0015). Maternal PEth 16:0/18:2 and 16:0/20:4 were\xa0~\xa025%↑ and\xa0~\xa020%↑ higher than in fetal blood (P\xa0<\xa00.05). No homologue differences were detected in the maternal uterine artery. In all fetal brain regions, PEth 16:0/18:1 was significantly higher (P\xa0<\xa00.0001) than 16:0/18:2 (~48-78%↑) and 16:0/20:4 (~31-62%↑) concentrations. PEth 16:0/20:4 was\xa0~\xa018% higher than 16:0/18:1 (P\xa0<\xa00.05) in the fetal hippocampus and cortex.\n\n\nCONCLUSION\nAll major PEth homologues were detected in maternal and fetal blood following chronic gestational binge alcohol exposure; homologue distribution profiles were tissue specific. This study also provides insights into PEth accumulation in critical FASD targets, specifically the maternal uterine artery and fetal brain.