The long-term goal of the applicant is to elucidate the mechanisms of placental amino acid metabolism and regulation using newly developed in vitro models. This knowledge will contribute to understanding the relationship between placental metabolism and normal fetal growth and development. The proposed study focuses on elucidating the pathways of placental metabolism of the quantitatively important amino acid glutamate. The human placenta accumulates glutamate to concentrations orders of magnitude above those in either maternal or fetal circulations and acts as a barrier to transplacental glutamate movement. The placenta may provide an important protective system for a compound which is a known fetal neurotoxin. Our fundamental hypothesis is that the glutamate concentrative activity is accompanied by a high rate of glutamate metabolism by the placenta and that the underlying metabolic pathways respond to environmental and regulatory mechanisms. Unique strengths of the project are that 1) it brings together the expertise of two laboratories, one experienced in trophoblast cell culture and cytologic investigation and the other experienced in the study of placental nutrient transport and metabolism 2) it the use of a trophoblast culture model which possesses previously unavailable features of cell differentiation to study metabolic pathways.
The specific aims of the project are: 1) Characterization of the trophoblast culture model. 2) Elucidation of the pathways of placental glutamate metabolism. 3) Characterization of regulatory factors of glutamate metabolism. 4) Elucidation of cellular features to support a putative fetal-placental substrate cycle involving glutamate.
The specific aims are directed toward achieving the long-term goal of the applicant which should help to increase chances for positive fetal outcomes.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
First Independent Research Support & Transition (FIRST) Awards (R29)
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Human Embryology and Development Subcommittee 1 (HED)
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Washington University
Schools of Medicine
Saint Louis
United States
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Prasad, P D; Hoffmans, B J; Moe, A J et al. (1996) Functional expression of the plasma membrane serotonin transporter but not the vesicular monoamine transporter in human placental trophoblasts and choriocarcinoma cells. Placenta 17:201-7
Moe, A J (1995) Placental amino acid transport. Am J Physiol 268:C1321-31
Prasad, P D; Ramamoorthy, S; Moe, A J et al. (1994) Selective expression of the high-affinity isoform of the folate receptor (FR-alpha) in the human placental syncytiotrophoblast and choriocarcinoma cells. Biochim Biophys Acta 1223:71-5
Moe, A J; Plas, D R; Powell, K A et al. (1994) Riboflavin uptake in microvillous and basal membrane vesicles isolated from full-term human placentas. Placenta 15:137-46
Moe, A J; Furesz, T C; Smith, C H (1994) Functional characterization of L-alanine transport in a placental choriocarcinoma cell line (BeWo). Placenta 15:797-802
Broeder, J A; Smith, C H; Moe, A J (1994) Glutamate oxidation by trophoblasts in vitro. Am J Physiol 267:C189-94
Furesz, T C; Smith, C H; Moe, A J (1993) ASC system activity is altered by development of cell polarity in trophoblast from human placenta. Am J Physiol 265:C212-7
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Moe, A J; Farmer, D R; Nelson, D M et al. (1991) Pentose phosphate pathway in cellular trophoblasts from full-term human placentas. Am J Physiol 261:C1042-7