CHRONIC ETHANOL EXPOSURE INHIBITS INSULIN AND IGF-1 STIMULATED AMINO-ACID-UPTAKE IN CULTURED HUMAN PLACENTAL TROPHOBLASTS

Maternal alcohol abuse during pregnancy can lead to abnormalities in f etal development, sometimes manifested as the fetal alcohol syndrome ( FAS). Although intrauterine growth retardation is a hallmark of FAS, t he pathophysiology is not fully understood. A contributing factor may be altered placental function. In this study, the effect of long-term exposure to ethanol on subsequent amino acid uptake by the cultured hu man placental trophoblasts was examined. Both Na+-dependent and Na+-in dependent pathways for AIB uptake were measured. As reported previousl y, insulin and IGF-1 enhanced Na+-dependent AIB uptake. Exposure to et hanol had no effect on basal (nonhormone treated) AIB uptake. However, 72-hr ethanol pretreatment of trophoblasts inhibited Na+-dependent AI B uptake under stimulation by insulin or IGF-1 in the absence of ethan ol. Na+-independent uptake was not affected. Ethanol treatment had no effect on insulin or IGF-1 binding to cultured trophoblasts. These fin dings suggest that 72-hr ethanol treatment in cultured trophoblasts ma y affect postreceptor signal transduction in the insulin or IGF-1 path ways. Such changes have implications for the effect of ethanol on norm al function of the human placenta, the major interface for maternal/fe tal transfer of nutrients.