| Maternal alcohol abuse during pregnancy can result in a range of structural and functional abnormalities that include lifelong physical, mental, behavioral and learning disabilities, now collectively termed as Fetal Alcohol Spectrum Disorders (FASD). The incidence of FASD is now estimated be as high as 10 per 1000 live births. Each year, 40,000 babies are born with FASD in the United States at an estimated cost of ;The present study was conducted using an ovine model system. The large body mass of the ovine fetus, the longer gestation that is more similar to that of humans, and that all three trimester equivalents occur in utero, make the sheep an excellent model to study the effects of alcohol on the developing fetus. Our study establishes that maternal alcohol exposure does not result in fetal cerebral hypoxia. Instead, alcohol results in hypercapnea and acidemia leading to a cascade of events in the maternal and fetal compartments that include deficits in the levels of glutamine and glutamine-related amino acids, alterations in endocrine axes, oxidative stress, alteration in cardiovascular homeostasis and fetal neuronal loss. Further, we demonstrate that inhibiting the novel two-pore domain acid sensitive potassium channel (TASK) expressed in the cerebellar granule cells and the peripheral and central chemoreceptors may prove to a be potential therapeutic strategy. Preventive strategies that are safe to use in pregnant women and that involve glutamine-related pathways are also suggested. Finally, the study also establishes the beneficial effects of moderate alcohol consumption on the fetal skeletal system. |
