The overall goal of this project is the investigation of the cellular physiology of the placental transfer of important nutrients and the regulation of these processes by mechanisms with the potential to operate in the intrauterine environment. During the forthcoming project period, investigations will focus on the transfer of amino acids, calcium and glucose. Amino acids are utilized by the fetus for growth and catabolism; glucose is a major fetal nutrient and calcium is essential for skeletal mineralization. The importance of these processes to the fetus the large quantities utilized, and the clinical importance of disorders of fetal growth and neonatal calcium metabolism all point to the importance of understanding the placental transfer of these substances. The strengths of the project are: (1) its use of well-characterized specific preparations of each of the two plasma membranes and of subcellular material from the syncytiotrophoblast, some of which were developed specifically for this project; (2) its relatively unique application to the placenta of established methods for the elucidation of cellular transport mechanisms whose utility has been proven in widely accepted reports from laboratories studying a variety of cellular and subcellular systems, (3) its application of cultured trophoblast using newly available preparations which permit investigation of the regulation of membrane transport mechanisms and their relation to trophoblast differentiation; (4) its introduction of molecular techniques to investigate the protein species of transporters and the cellular machinery for their synthesis.
Specific aims i nclude the characterization and comparison of calcium transport mechanisms of the syncytial microvillous and basal plasma membranes and cytoplasm; the characterization of amino acid transport systems and glucose transporters of the two plasma membranes; the development of cultured trophoblast as a model to investigate amino acid, calcium, and glucose transport; and the investigation of the regulation of trophoblast mechanisms for calcium, amino acid, and glucose transport.
