The overall objective of this project is to characterize the molecular bases which underlie placental transfer of nutrients from human mother to fetus. Within this objective, we have been concerned primarily with transfer by the glucose transporter. We have obtained evidence that the reversibly oxidized form of vitamin C, dehydroascorbic acid, is transferred across the microvillous membrane of the syncytiotrophoblast by the sodium- independent, glucose transporter. In contrast, the reversibly reduced form of vitamin C, L-ascorbic acid, does not appear to cross this membrane by the glucose transporter but does not synthesize vitamin C, placental transfer is of fundamental importance in normal fetal development. Thus, the specific aims of this proposal are to further characterize the role of the glucose transporter by mechanisms other than the glucose transporter and simple diffusion. The latter aim is particularly important in elucidating the mechanism(s) by which the human fetus maintains blood concentration of vitamin C which are several times that of the mother.
These aims will be addressed experimentally using membrane vesicles derived from the microvillous and basal sides of the syncytiotrophoblast. These studies have already, and will continue to shed light on the functional specificity of the human placental glucose transporter as well as lead to a better mechanistic understanding of maternal-fetal transfer of a metabolically important vitamin.