Ethanol Exposure Increases Oxygen Consumption by Developing Cerebral Arteries in a Trimester-, Concentration- and Sex-Dependent Manner

Alcohol (ethanol; EtOH) intake affects one in ten pregnancies in the United States and is a leading cause of developmental defects collectively known as fetal alcohol spectrum disorders (FASDs). Cerebral circulation is a critical target of prenatal ethanol exposure (PEE), yet the target(s) involved remain poorly understood. In adult cerebral circulation, mitochondrial function is essential in regulating smooth muscle contractility, suggesting mitochondria as a potential target of alcohol in the developing cerebral arteries. In this study, pregnant C57BL/6J mice were administered ethanol (3, 4.5, 6, or 7 g/kg) during either the second trimester equivalent of human pregnancy (gestational days 9–19), or the third trimester equivalent during postnatal days 1–10. Maternal and progeny blood ethanol concentrations, progeny brain weight, cerebral artery oxygen consumption, and corticosterone levels were measured. At lower ethanol concentrations (3 g and 4.5 g/kg), no significant alterations in fetal cerebral artery mitochondrial function were detected. In contrast, heavy maternal ethanol exposure (6 g/kg) significantly increased mitochondrial respiratory parameters in developing cerebral arteries during the third trimester equivalent of human pregnancy. Sex-specific dimorphism was also observed at this developmental stage. Corticosterone was not elevated in fetuses and pups. In summary, our findings demonstrate developmental stage- and sex-dependent vulnerabilities of cerebrovascular oxygen consumption to ethanol exposure.