Ethanol can cause serious fetal abnormalities, including intrauterine growth retardation (IUGR), microcephaly and mental retardation. While ethanol may be directly toxic to the fetus, it may also injure the placenta. The placenta is the sole conduit for fetus' supply of nutrients critical to normal growth and development. It is postulated that the placenta plays an important role in ethanol- related fetal injury through: (1) ethanol-associated impairment of placental function, thereby restricting placental transfer of nutrients and production of hormones essential to fetal growth and (2) placental production and transfer of acetaldehyde, thereby exposing both the fetus and the placenta to additional injury. One objective is to characterize the effects of ethanol or ethanol plus acetaldehyde upon human placental transport of nutrients: amino acids, glucose, vitamins (thiamine, riboflavin), zinc. The influence of ethanol upon placental stimulation of fetal growth and maintenance of an adequate maternal supply of glucose and amino acids will be assessed by measuring placental synthesis of growth hormone releasing factor and human placental lactogen. Models for studying ethanol-related impairment of placental function will include the human isolated perfused placental cotyledon and human placental membrane vesicles. Nutrient transport, hormone synthesis and membrane fluidity changes will be studied with respect to different ethanol doses, at levels achievable in humans. Animals will be used to study chronic effects under controlled conditions, although placentae from chronic alcoholic humans will be obtained for evaluation. The second objective is to identify the extent to which the placenta produces the toxic metabolite of ethanol, acetaldehyde, and the extent to which it transfers maternal blood acetaldehyde to the fetal circulation. Placental metabolism of ethanol will be assessed under intact organ conditions (perfused placenta) and by biochemical analysis. Placental production of acetaldehyde may be a compounding factor in the pathogenesis of ethanol-induced placento-toxicity as well as feto-toxicity. With improved definition of the effects of ethanol upon several parameters of placental function, it should be possible to better understand the pathophysiology of some of the clinical manifestations of ethanol upon several parameters of placental function, it should be possible to better understand the pathophysiology of some of the clinics manifestations of ethanol- related injury, such as IUGR and mental retardation. The use of modest and high physiologic ethanol levels in the experiments, plus the extensive use of human tissue should make the findings more pertinent to the human circumstance.
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