In Vivo Placental Transport of Glycine and Leucine in Human Pregnancies

Cetin, Irene; Marconi, Anna Maria; Baggiani, Anna Maria; Buscaglia, M; Pardi, Giorgio; Fennessey, Paul V.; Battaglia, Frederick C.

doi:10.1203/00006450-199505000-00002

Cited by 66 publications

(29 citation statements)

References 17 publications

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“…Leucine has been shown to be an effective stimulus for fetal insulin in human fetal pancreas studied in vitro (18). In addition, in vivo studies applying stable isotope techniques have provided evidence to suggest that leucine taken up across the MVM is rapidly transferred to the fetus (45). Therefore, we suggest that the increased leucine transport across the MVM in the GDM/LGA group increases the leucine delivery to the fetus and contributes to the accelerated fetal growth in these patients.…”

Section: Discussionmentioning

confidence: 91%

Alterations in the Activity of Placental Amino Acid Transporters in Pregnancies Complicated by Diabetes

et al. 2002

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Alterations in placental transport may contribute to accelerated fetal growth in pregnancies complicated by diabetes. We studied the activity of the syncytiotrophoblast amino acid transporter system A and the transport of the essential amino acids leucine, lysine, and taurine. Syncytiotrophoblast microvillous plasma membranes (MVMs) and basal plasma membranes (BMs) were isolated from placentas obtained from normal pregnancies and pregnancies complicated by gestational diabetes mellitus (GDM) and type 1 diabetes, with and without large-for-gestational-age (LGA) fetuses. Amino acid transport was assessed using radio-labeled substrates and rapid filtration techniques. System A activity in MVM was increased (65-80%, P < 0.05) in all groups with diabetes independent of fetal overgrowth. However, MVM system A activity was unaffected in placentas of normal pregnancies with LGA fetuses. MVM leucine transport was increased in the GDM/LGA group. In BMs, amino acid transport was unaffected by diabetes. In conclusion, diabetes in pregnancy is associated with an increased system A activity in MVM, and MVM leucine transport is increased in the GDM/LGA group. We suggest that these changes result in an increased uptake of neutral amino acids across MVM, which may be used in placental metabolism or be delivered to the fetus. The increased MVM leucine uptake in the GDM/LGA group may contribute to accelerated fetal growth in these patients.

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Section: Discussionmentioning

confidence: 91%

Alterations in the Activity of Placental Amino Acid Transporters in Pregnancies Complicated by Diabetes

et al. 2002

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“…During the second half of gestation, increasing placental surface area does not match the increase in fetal size, therefore increasing amino acid transporter abundance and capacity is necessary for appropriate fetal growth. In addition, in vivo human and sheep studies have shown that many amino acids transferred to the fetus are produced in the placenta through interconversion of metabolically related amino acids [111,112].…”

Section: Placental Amino Acid Transfer and Metabolismmentioning

confidence: 99%

The pregnant sheep as a model for human pregnancy

2008

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Successful outcome of human pregnancy not only impacts the quality of infant life and well-being, but considerable evidence now suggests that what happens during fetal development may well impact health and well-being into adulthood. Consequently, a thorough understanding of the developmental events that occur between conception and delivery is needed. For obvious ethical reasons, many of the questions remaining about the progression of human pregnancy can not be answered directly, necessitating the use of appropriate animal models. A variety of animal models exist for the study of both normal and compromised pregnancies, including laboratory rodents, non-human primates and domestic ruminants. While all of these animal models have merit, most suffer from the inability to repetitively sample from both the maternal and fetal side of the placenta, limiting their usefulness in the study of placental or fetal physiology under non-stressed in vivo conditions. No animal model truly recapitulates human pregnancy, yet the pregnant sheep has been used extensively to investigate maternal-fetal interactions. This is due in part to the ability to surgically place and maintain catheters in both the maternal and fetal vasculature, allowing repeated sampling from non-anesthetized pregnancies. Considerable insight has been gained on placental oxygen and nutrient transfer and utilization from use of pregnant sheep. These findings were often confirmed in human pregnancies once appropriate technologies became available. The purpose of this review is to provide an overview of human and sheep pregnancy, with emphasis placed on placental development and function as an organ of nutrient transfer.

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“…This establishes the fact that in the fetal sheep, serine requirements must be met by endogenous fetal serine production. A recent study suggests that a similar situation exists in the human fetus (24). Several studies have led to the hypothesis of interorgan cycling between the the placenta and the fetus (particularly the fetal liver) for these two amino acids (2,23).…”

Section: ---------------------mentioning

confidence: 94%

Pathways of Serine and Glycine Metabolism in Primary Culture of Ovine Fetal Hepatocytes

Thureen¹,

Narkewicz²,

Battaglia³

et al. 1995

Pediatr Res

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Previous in vivo studies in the ovin e fetus have demonstrat ed net serin e production by the fetal liver, a pattern not seen in the adult sheep. The goal of this study was to determine the major metabolic pathway s responsible for fetal hepatic serine production by using stable isotop e methodology in primary culture of late ges tation ovine fetal hepatocytes. Specificall y selected tracers of glycine were added to individual cultures, with production of labeled serine determin ed after 24 h of incubati on. When [1-13 C ,lglycine or [2-13 C 1 ]glycine was used as the initial tracer , serine enrichment at 24 h indic ated that approximately 30% of serine production comes from glycine. Quantitative comparison of serin e enrichme nt from these two tracers suggests that serine synthesis from glycine occurs via the combined action of the glycine cleavage enzyme system (GCE) and serine hydrox ymethyltransferase (SHMT). Using [1,2-13 C:z J5 N 1 ]glycine as the tracer, there was no sig nificant increase in M + 2 glycine in the During fetal life, amino acids are used for many functions such as precursors for prote in synthesis and metab olic fuel s, and for the sy nthesis of other carbon-and nitrogen-containing compounds including nucleic acids, glyco gen, and lipid. There is increasing evidence that fetal amino acid metabolism has unique char acteristics when compared with adult metabolism (1, 2). Som e of these differences are due to ontologie changes in organ-specific amino acid metabolism (3). In particular, there appea r to be differences in fetal hepatic serin e metabolism when compared with adult hepatic serine metabolism (2, 4-8). In the sheep, in vivo studi es have indicated that serine and glycin e have unique fetal metabolic characteristics compared with those that have been demonstrated in adult animals of other species. Using the unique abilit y to chronically catheterize the ov ine fetal liver, it has been demonstrated that in the

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In Vivo Placental Transport of Glycine and Leucine in Human Pregnancies

Cited by 66 publications

References 17 publications

Alterations in the Activity of Placental Amino Acid Transporters in Pregnancies Complicated by Diabetes

Alterations in the Activity of Placental Amino Acid Transporters in Pregnancies Complicated by Diabetes

The pregnant sheep as a model for human pregnancy

Pathways of Serine and Glycine Metabolism in Primary Culture of Ovine Fetal Hepatocytes

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