The placenta is vital to the survival of the fetus because it provides the growing fetus with nutrition and oxygen and it excretes the fetal metabolic waste products. Several classes of nutrients are transferred from the mother to the fetus across the placenta. Interference with this function of the placenta invariably results in growth retardation of the fetus and reduces its chances of survival. Therefore, there is a profound need for information relating to the role of the placenta as a nutritional organ. Amino acids represent an important class of nutrients because they are obligatory as the building blocks for protein synthesis and as precursors for many biologically active compounds which are vital to the well-being of the fetus. Most amino acids are transported across the placenta by energy-dependent processes. The energy-requiring step is primarily located at the brush border membrane of the placenta. The proposed studies will therefore be conducted by using brush border membrane vesicles isolated from human term placentas. Human placenta is a disposable tissue and use of this tissue as the experimental tool offers a unique opportunity to investigate placental function without safety and ethical concerns. Moreover, direct use of the human placentas rather than the placentas from laboratory animals removes the need for unnecessary, and sometimes even incorrect and misleading, extrapolation of the results from non-human species to humans. Virtually nothing is known at present about the molecular mechanisms of amino acid transfer across the placenta. This project proposes a series of investigations designed to look into this aspect.
The specific aims of the project include delineation of the role of ion gradients other than a sodium gradient as the energy source for placental amino acid transport, determination of the chemical nature of the active site of amino acid transport systems, and purification and characterization of the proteins which make up these transport systems. Substances such as ethanol, cannabinoids and various drugs interfere with placental amino acid transport and consequently have toxic effects on fetal growth and development. A detailed knowledge of the chemical nature of the placental amino acid transport systems is not only important to understand the placenta amino acid transfer under physiological conditions, but also to understand the mechanisms by which the above- mentioned feto-toxic agents affect the function of these transport systems.
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