This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Intrauterine growth restriction represents one of the most important causes of perinatal morbidity and mortality. In recent years, there has been an increased focus on the specific defect of a reduction in amino acid transport across the placenta in IUGR pregnancies. A reduction in placental transport of amino acids has been shown in growth retarded human pregnancies, both at the time of in utero fetal blood sampling and at Cesarean section. These findings are supported by in vitro studies of placentas from pregnancies complicated by IUGR. A specific reduction in these pregnancies has been shown for amino acids transported by System A (1). While there have been numerous studies of amino acid transport in perfused human placentas (2-4) and in our microvesicle preparations of the placenta (5,6), in vivo transport characteristics have not been described. In vivo studies carried out in pregnant sheep recently in our laboratory have shown striking differences in the rates of in vivo transport among the nine essential amino acids (15). The goal of the present study is to analyze the in vivo transport for all essential amino acids. It is our belief that these studies should identify an essential amino acid that would be a sensitive index of placental failure and in the long term may provide an additional very useful guide in the management of IUGR pregnancies. Human pregnancies complicated by IUGR have been shown to have abnormal placental vasculature [17-23] including abnormal branching patterns. Human placental vascular casts have been imaged using scanning electron microscopy (SEM) in both normal and pathologic placentas. Characteristic vascular changes have been observed, but there is little clinical correlation with doppler studies and clinical terms are often inconsistent or confusing. The placenta is a heterogeneous organ and SEM of vascular casts may be representative of focal changes only. As a second goal of this study we wish to evaluate the use of two techniques, barium-gelatin arteriograms (24) and serial tissue sections that have been reconstructed using 3-dimesional imaging software (25), to see if these could be useful tools in the evaluation of the placental vasculature in human pregnancies complicated by IUGR.
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