Colorado PROFILES, The Colorado Clinical and Translational Sciences Institute (CCTSI)
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Fetoplacental amino acid metabolism in IUGR pregnancies

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Intrauterine growth restriction (IUGR) is an important and relatively common problem in obstetrics. It contributes markedly to fetal and neonatal pathology and poor reproductive outcome, as well as adult pathology including a higher incidence of diabetes and hypertension. Fetal IUGR often results from impaired placental function and insufficient to meet demand for nutrients, and fetal adaptation to that placental function and insufficiency to meet fetal demands for nutrients, and fetal adaptation to that insufficiency. Studying the developing placenta and fetus is extremely important, therefore, in expanding our knowledge on fetomaternal interactions, prior to, and during the development of an IUGR fetus. We have developed an ovine model for IUGR that results from placental insufficiency (PI), created by exposure of pregnant ewes to a hypothermic environment during the period of maximal placental growth and development (40-120 dGa, term 147+/- 3 days). This model shares many of the physiological and biochemical characteristics documented in human IUGR pregnancies, including reduced fetal weight, asymmetrical growth, changes in glucose and amino acid metabolism, as well as velocimetry changes in the fetal circulation. The objective of this project is to determine the changes in placental vasculature, placental exchange surface area and fetoplacenta- interorgan exchange of essential and anionic amino acids during the period of maximal fetal growth (last third of pregnancy) in a model fo PI-IUGR. We propose that reductions in vilious exchange surface area and independent reductions in essential and anionic amino acid transporters contribute to the development of IUGR. We will test for differences in essential and anionic amino acid transport in vivo, as well as the expression and location of several transporters (y+, y+1, N and XAG) in vitro, in normal and IUGR placenta. We will report amino acid transport n terms of per unit tissue, and the expression data per surface area unit. We will also test for differences between normal and IUGR placentae for alterations in fetoplacental anionic amino acid transport and correlative interactions of members of the insulin-like growth factor (IGF) family in the development of the XAG system. The information provided by these studies is necessary to identify potential compensatory mechanisms in PI-IUGR pregnancies, which could lead to possible therapeutic approaches to improve placental-fetal nutrient exchange, placental growth and fetal growth.
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