Maternal to fetal transfer of free fatty acids in the in situ perfused rabbit placenta

The transfer of free fatty acids (FFA) across the placenta perfused in situ was studied in anaesthetised rabbits in late gestation. [14C]Palmitic acid and antipyrine were infused into 11 pregnant rabbits and samples collected for up to 90 min from the mother and the umbilical vessels. Levels of total FFA, radioactivity and antipyrine, a marker of placental integrity, were measured. Net FFA flux across the placenta increased with maternal FFA concentrations, confirming observations made using different methods. The specific activity of [14C]palmitic acid in perfusate also related to maternal levels and indicated that almost half of the FFA crossing the rabbit placenta must be derived from sources other than circulating maternal FFA. The composition of the perfusate FFA had a profile similar to that of circulating maternal FFA, except for an increase in a number of long chain, polyunsaturated fatty acids. These findings are consistent with maternal triacylglycerol as the other fatty acid source, with the placenta adding the longer chain, polyunsaturated fatty acids.     

The interrelationships between circulating maternal esterified and non-esterified fatty acids in pregnant guinea pigs and their relative contributions to the fetal circulation

The relative contributions of esterified and non-esterified fatty acids to placental lipid transfer were estimated in 7 pregnant guinea-pigs. The fetal side of the placenta was perfused in situ whilst a constant infusion of a mixture of [3H]triacylglycerol emulsion (Intralipid) and [14C]non-esterified fatty acid was given i.v. to the anaesthetised mother. Considerable interconversion of the lipid moieties circulating in the mother was observed. Metabolic turnover rates of triacylglycerol and non-esterified fatty acid were found to be 14.6 mmol/day and 55 mmol/day respectively. No intact triacylglycerol was found to cross the placenta from the mother. Relatively more [3H]non-esterified fatty acid than [14C]non-esterified fatty acid was found in the perfusion fluid when compared with simultaneous circulating maternal levels of these non-esterified fatty acids indicating hydrolysis and direct transfer of [3H]triacylglycerol within the placental tissue. This hydrolysis resulted in the transfer of approximately 0.2 mmol non-esterified fatty acid/day across each placenta at this gestational age (53 days). This is in contrast to the transfer of circulating maternal non-esterified fatty acids, these can be calculated to give a mother to fetus unidirectional transport value of 3.62 mmol/day/placenta, but the total maternal to fetal flux taking into account back transfer to the mother is 1.26 mmol/day/placenta. Results from simultaneous carotid artery and uterine vein samples showed that approximately 40% of the maternal arterial triacylglycerol is removed during a pass through the uterine bed, but the majority of the triacylglycerol re-emerges in the uterine vein as non-esterified fatty acids, and masks the uterine vein uptake of circulating maternal non-esterified fatty acid. The uterine vein non-esterified fatty acid concentration is highly dependent upon levels of circulating maternal triacylglycerols and apparent uterine bed production of non-esterified fatty acid occurs when maternal triacylglycerols are high relative to non-esterified fatty acids.     

Placental transport of free palmitic and linoleic acids in the guinea pig

Radioisotopic tracers were used to measure the unidirectional transfer rates of free fatty acids across the placenta of fed and fasted pregnant guinea pigs. Free (14)C-labeled palmitic and linoleic acids (in serum) were injected simultaneously into a jugular vein of an anesthetized pregnant guinea pig. Serial samples of maternal blood were collected from a carotid artery; fetal blood was collected from the umbilical vein of an exposed fetus. Analysis of maternal and fetal plasma revealed that: (a) the half-lives of free palmitic and linoleic acid in maternal plasma are approximately 1.3 min and 0.7 min, both in fed animals with low plasma concentrations of these acids and in fasted animals with high concentrations; (b) free linoleic and palmitic acids cross the placenta from maternal to fetal plasma in a ratio of approximately 2.0, a value which appears not to change as the transfer rates of these acids from maternal to fetal plasma are increased by fasting the mother. It is suggested that the ratio in which free linoleic and palmitic acids cross the placenta from maternal to fetal plasma is determined by the ratio of the unbound free linoleic and palmitic acid concentrations in maternal plasma. A comparison of several species indicates that a much greater proportion of fetal fatty acids comes from the mother in the guinea pig and rabbit than in the rat, the sheep, or man.     

A potential role for lysophosphatidylcholine in the delivery of long chain polyunsaturated fatty acids to the fetal circulation

The mechanisms of placental transfer of long chain polyunsaturated fatty acids are poorly understood, however fatty acid transporters in the syncytiotrophoblast microvillous (MVM) and basal plasma membrane (BM) are believed to be involved. Using LC-MS/MS and samples from normal term pregnant women, we found that the concentration of lysophosphatidylcholine-docosahexaenoyl (DHA-LPC) was 4-fold higher in umbilical vein plasma compared to maternal venous concentrations while conversely phosphatidylcholine (PC) containing DHA or arachidonic acid were higher in maternal circulation. Using primary human trophoblast cells incubated with DHA we show that DHA was highly incorporated into PC and LPC species in the placenta. Protein expression of Phosphatidylcholine Transfer Protein (PCTP) was 14-fold higher in MVM and the expression of MFSD2a, an LPC transporter, was 5-fold higher in BM than in MVM. Interestingly, BM MFSD2a expression was positively correlated with DHA-LPC in the umbilical vein. These findings suggest that syncytiotrophoblast takes up PC from the maternal circulation, as well as preferentially incorporating DHA into PC. Placental PC are converted to LPC forms, which are transported across the BM mediated by MFSD2a, with a strong selectivity for DHA.     

Effect of plasma free fatty acid concentration on the content and composition of the free fatty acid fraction in rat skeletal muscles.

Skeletal muscles contain a fraction of free (unesterified) fatty acids. This fraction is very small, but important since it contributes to the creation of the plasma-myocyte free fatty acid concentration gradient. Maintenance of this gradient is necessary for blood-borne fatty acids to be transported into the cell. There are no data on the regulation of the content and composition of the free fatty acid fraction in the cell. The aim of the present study was to examine the effect of an elevation and a reduction in the plasma-borne free fatty acid concentration on the content and composition of the free fatty acid fraction in different skeletal muscle types. The experiments were carried out on male Wistar rats with 280 - 310 g body weight. They were divided into four groups - 1, control; 2, exercised 3 h on a treadmill moving with a speed of 1,200 m/h and set at + 10 degrees incline; 3, treated with heparin; and 4, treated with nicotinic acid. Samples of the soleus as well as the red and white sections of the gastrocnemius muscles were taken. These muscles are composed mostly of slow-twitch oxidative, fast-twitch oxidative-glycolytic and fast-twitch glycolytic fibres, respectively. Lipids were extracted from the muscle samples and from the blood; the free fatty acid fraction was isolated by means of thin-layer chromatography. The individual free fatty acids were identified and quantified using gas-liquid chromatography. The plasma concentration of free fatty acids was as follows: control group, 236.1 +/- 32.9; after exercise, 407.4 +/- 117.5; after heparin, 400.8 +/- 36.8; and after nicotinic acid, 102.5 +/- 26.1 micromol/l (p < 0.01 vs. control values in each case). The total content of the free fatty acid fraction in the control group was as follows: white gastrocnemius, 27.6 +/- 7.3; red gastrocnemius, 52.2 +/- 13.9; soleus, 72.3 +/- 10.2 nmol/g. Elevation in plasma free acid concentration during exercise increased the total content of free fatty acids in the white gastrocnemius (38.7 +/- 13.9) and in the soleus (103.4 +/- 15.9 nmol/g; rest-exercise: p < 0.05 and p < 0.01, respectively), but had no effect in the red gastrocnemius. Neither elevation in the plasma free fatty acid concentration with heparin nor reduction with nicotinic acid affected the total content of the free fatty acid fraction in the muscles examined. The ratio of plasma concentration of individual acid to muscle concentration for the same acid varied greatly, depending on acid, muscle type and experimental group. The ratio was positive (above unity) for each acid almost in all cases with the exception of certain acids in the nicotinic acid-treated group where it was below unity. We conclude that the skeletal myocytes maintain a stable level of free fatty acid fraction in the wide range of plasma free fatty acid concentrations.     

The relationship of umbilical glucose uptake to uterine blood flow

In 30 experiments performed on 5 pregnant sheep, the rate of glucose transfer from the placenta to fetus via the umbilical circulation was measured while varying uterine blood flow by means of a cuff-type occluder and while maintaining a constant maternal glucose concentration by means of a 'glucose clamp'. Over the range of uterine blood flows obtained, there was no significant effect on the simultaneously measured umbilical blood flow. Fetal glucose uptake and arterial glucose concentration remained normal as the uterine blood flow rate decreased from 600 to 300 ml per min per kg of fetus. At blood flow rates less than 300 ml.min-1.kg-1, the fetal glucose uptake decreased and became negative in one instance while the arterial glucose concentration became variable and markedly increased in 2 animals. This increase in fetal glucose concentration was associated with a decrease in the uterine oxygen delivery rate, a decrease in fetal oxygen content and a decrease in fetal oxygen uptake. These observations support the concept that fetal glucose metabolism is altered by severe hypoxia and demonstrate that there is little effect of uterine blood flow on fetal glucose uptake in the normal physiological range.     

The transfer of fatty acids across the sheep placenta

Maternal and fetal plasma concentrations of free fatty acids, triacylglycerols and phospholipids and the profile of their fatty acids were measured in three catheterized and unanaesthetized sheep. Fetal concentrations of all three lipid fractions were low and did not correlate with maternal concentrations. There were no measurable umbilical venous-arterial differences. Linoleic acid concentrations were low in both mother and fetus. The fatty acid composition of fetal adipose tissue, liver, lung and cerebellum of five animals was analysed. Again linoleic acid levels were very low, but phospholipids contained 2-8% arachidonic acid. [14C] linoleic acid and [3H] palmitic acid were infused intravenously into three ewes. Only trace amounts of labelled fatty acids were found in fetal plasma and these were confined to the free fatty acids. 14C-label was incorporated into fetal tissue lipids, but most of this probably was due to fetal lipid synthesis from [14C] acetate or other water-soluble products of maternal [14C] linoleic acid catabolism. It is concluded that only trace amounts of fatty acids cross the sheep placenta. They are derived mainly from the maternal plasma free fatty acids and might just be sufficient to be the source of the small amounts of essential fatty acids found in the lamb fetus, but are insignificant in terms of energy supply or lipid storage.     

Reciprocal inhibition of umbilical uptake within groups of amino acids

Eight pregnant sheep were infused with two amino acid mixtures of different composition: essential amino acids only and the essentials plus some of the nonessentials. Uterine and umbilical uptakes of amino acids were measured before and during infusion. For most of the amino acids, the infusion increased both maternal plasma concentration and umbilical uptake. However, depending on the infusate composition, the increase in maternal concentration of some amino acids was associated with no change or a significant reduction in umbilical uptake. Data were pooled from this and other, similar studies to test the hypothesis that umbilical uptake of several amino acids can be inhibited by coinfused amino acids. The test consisted of fitting the data, by means of multiple regression analysis, to the linear transformation of a saturation kinetics equation in which uptake is assumed to depend on maternal arterial concentrations. The analysis showed significant inhibitory effects within the neutral essential amino acids group and within the lysine-arginine group, with no demonstrable interaction between the two groups. Uterine uptakes did not show clear evidence of saturability and inhibitory interactions, suggesting a large transport capacity and low transporter affinity on the maternal surface of the trophoblast. We conclude that the transport of any given amino acid from placenta to fetus is a function of both its own maternal concentration and the maternal concentration of inhibitory amino acids.     

Maternal and umbilical fatty acid status in relation to maternal diet

The aim of this study was to describe the dietary fat intake during pregnancy and to study the relationship between the intake of polyunsaturated fatty acids (PUFAs) and the fatty acid composition of maternal and umbilical plasma phospholipids (PLs) and cholesterol esters (CEs) at delivery. In addition, the contribution of food groups to the intake of total fat and fatty acids in the diet was quantified.Maternal and umbilical blood samples were collected at delivery from 30 healthy pregnant women. The women completed a food frequency questionnaire during the first and third trimesters. The total fat intake during pregnancy is 85 (SD 24) g/day. The mean intake of saturated fatty acids (SFAs) is 33.4 g/day, of monounsaturated fatty acids (MUFAs) 28.6 g/day and of PUFA 15.2 g/day. Major sources of fat, MUFA and PUFA are fats, oils and sauces. Major sources of SFA are meat and poultry followed by cheese and eggs. Meat and poultry contribute the most to the intake of 20:4n-6 whereas fish is the major source of 20:5n-3 (EPA) and 22:6n-3 (docosahexaenoic acid (DHA)) in the diet. Linoleic acid, EPA and DHA (w%) in PL of maternal plasma are positively related to the intake of these fatty acids during pregnancy. No association is found between the maternal intake of the two parent essential fatty acids (18:2n-6 and 18:3n-3) and their fraction in umbilical PL or CE. EPA and the sum of n-6 fatty acids (w%) in umbilical plasma PL are positively correlated with the dietary intake of these fatty acids.     

The placenta releases branched-chain keto acids into the umbilical and uterine circulations in the pregnant sheep

There was net uptake of branched-chain keto acids by the fetus from the umbilical circulation. Mean fetal uptake of the 3 keto acids 2-keto isovalerate, 2-keto isocaproate and 2-keto methylvalerate was 1.8 mumol/min per kg of fetus. The concentrations in the umbilical vein for these keto acids were 10.9 +/- 3.8 microM (mean +/- SD: 2-keto isovalerate), 19.7 +/- 6.1 microM (2-keto isocaproate) and 14.8 +/- 5.3 microM (2-keto methylvalerate) respectively. The coefficients of extraction for the same keto acids were 17.2%, 16.8% and 11.9% respectively. Fetal uptakes (both mumol/min and mumol/min per kg fetus) were positively correlated with umbilical supply. There were concentration gradients across the placenta, with fetal concentration: maternal concentration ratios of 3.3 +/- 1.5 for 2-keto isovalerate, 2.1 +/- 0.8 for 2-keto isocaproate and 1.3 +/- 0.6 for 2-keto methylvalerate. The net release of 2-keto acids into the umbilical circulation may conserve the carbon skeleton of branched-chain amino acids for fetal metabolism and growth. In the uterine circulation there was not a consistent pattern of release from or uptake by the uteroplacental tissues. It is suggested that branched-chain keto acids may contribute to fetal growth or energy metabolism.     

Sex-specific responses in placental fatty acid oxidation,esterification and transfer capacity to maternal obesity

Fatty acid metabolism and oxidation capacity in the placenta, which likely affects the rate and composition of lipid delivered to the fetus remains poorly understood. Long chain polyunsaturated fatty acids, such as docosahexaenoic acid (DHA), are critical for fetal growth and brain development. We determined the impact of maternal obesity on placental fatty acid oxidation, esterification and transport capacity by measuring PhosphatidylCholine (PC) and LysoPhosphatidylCholine (LPC) containing DHA by mass spectrometry in mother-placenta-baby triads as well as placental free carnitine and acylcarnitine metabolites in women with normal and obese pre-pregnancy BMI. Placental protein expression of enzymes involved in beta-oxidation and esterification pathways, MFSD2a (lysophosphatidylcholine transporter) and OCTN2 (carnitine transporter) expression in syncytiotrophoblast microvillous (MVM) and basal (BM) membranes were determined by Western Blot. Maternal obesity was associated with decreased umbilical cord plasma DHA in LPC and PC fractions in male, but not female, fetuses. Basal membrane MFSD2a protein expression was increased in placenta of males of obese mothers. In female placentas, despite an increased MVM OCTN2 expression, maternal obesity was associated with a reduced MUFA-carnitine levels and increased esterification enzymes. We speculate that lower DHA-PL in fetal circulation of male offspring of obese mothers, despite a significant increase in transporter expression for LPC-DHA, may lead to low DHA needed for brain development contributing to neurological consequences that are more prevalent in male children. Female placentas likely have reduced beta-oxidation capacity and appear to store FA through greater placental esterification, suggesting impaired placenta function and lipid transfer in female placentas of obese mothers.     

Transfer of maternal plasma free fatty acids into the rat fetus.

The amount of maternal plasma free fatty acids passing to the fetus has been determined to be 0.09 mumoles fatty acids per min per each litter. Taking account of the increase of the total fetal fatty acid pool due to the fetal growth (0.2 mumoles fatty acids per min for each litter) we conclude that the maternal circulation is the source of about half of fetal fatty acids on day 21 of pregnancy.     

Placental Glucose Transfer: A Human In Vivo Study

ObjectivesThe placental transfer of nutrients is influenced by maternal metabolic state, placenta function and fetal demands. Human in vivo studies of this interplay are scarce and challenging. We aimed to establish a method to study placental nutrient transfer in humans. Focusing on glucose, we tested a hypothesis that maternal glucose concentrations and uteroplacental arterio-venous difference (reflecting maternal supply) determines the fetal venous-arterial glucose difference (reflecting fetal consumption).MethodsCross-sectional in vivo study of 40 healthy women with uncomplicated term pregnancies undergoing planned caesarean section. Glucose and insulin were measured in plasma from maternal and fetal sides of the placenta, at the incoming (radial artery and umbilical vein) and outgoing vessels (uterine vein and umbilical artery).ResultsThere were significant mean (SD) uteroplacental arterio-venous 0.29 (0.23) mmol/L and fetal venous-arterial 0.38 (0.31) mmol/L glucose differences. The transplacental maternal-fetal glucose gradient was 1.22 (0.42) mmol/L. The maternal arterial glucose concentration was correlated to the fetal venous glucose concentration (r = 0.86, p<0.001), but not to the fetal venous-arterial glucose difference. The uteroplacental arterio-venous glucose difference was neither correlated to the level of glucose in the umbilical vein, nor fetal venous-arterial glucose difference. The maternal-fetal gradient was correlated to fetal venous-arterial glucose difference (r = 0.8, p<0.001) and the glucose concentration in the umbilical artery (r = −0.45, p = 0.004). Glucose and insulin concentrations were correlated in the mother (r = 0.52, p = 0.001), but not significantly in the fetus. We found no significant correlation between maternal and fetal insulin values.ConclusionsWe did not find a relation between indicators of maternal glucose supply and the fetal venous-arterial glucose difference. Our findings indicate that the maternal-fetal glucose gradient is significantly influenced by the fetal venous-arterial difference and not merely dependent on maternal glucose concentration or the arterio-venous difference on the maternal side of the placenta.     

Maternal plasma triglycerides as a source of fetal fatty acids.

The transfer of plasma triglyceride fatty acids from mother to fetus was studied in rats. Following i.v. injection of labelled chylomicron and very low density lipoprotein (VLDL) triglycerides into the mother, the time courses of the plasma triglycerides, free fatty acids, and fetal radioactivity were determined. The data were analysed using a mathematical model. From the results the following conclusions were drawn: To cover the need of fetal fatty acids, the placenta utilizes only VLDL triglycerides but not chylomicron triglycerides. Comparison of the amount of VLDL triglyceride fatty acids (0.04 micromoles/min/litter) and of maternal plasma free fatty acids (0.08 micronmoles/min/litter) transferred into the fetus indicates that the maternal plasma triglycerides are a source of fetal fatty acids, that cannot be neglected.     

Lipid compounds of the umbilical cord vein and their alterations in preeclampsia

The lipid composition of vascular walls changes during development, ageing and pathological processes. Preeclampsia is the most common pregnancy-associated pathological syndrome. It is accompanied by significant remodelling of the extracellular matrix, both in the umbilical cord vessels and in the surrounding Wharton's jelly. Lipids of the umbilical cord have not been extensively studied. Here we evaluate the lipid composition of the umbilical cord vein and its alteration in preeclampsia. Thin layer chromatography and high-performance liquid chromatography were employed for these analyses. It was found that the umbilical cord vein wall, as with most human tissues, contains free fatty acids, mono-, di- and triacylglycerols, free cholesterol and its esters. The characteristic feature is the presence of high amounts of monounsaturated fatty acids, mainly myristoleic acid (C14:1) and oleic acid (C18:1), and polyunsaturated fatty acids, including eicosapentaenoic acid (C20:5) and docosahexaenoic acid (C22:6), which are rather minor lipid components of most human tissues. They exist both in a free form and in a form of acylglycerols and cholesterol esters. Preeclampsia is associated with an increase in the accumulation of free fatty acids, acylglycerols and cholesterol esters in the umbilical cord vein wall, with a proportional reduction in unsaturated fatty acid contents in all the investigated lipid fractions. Total amount of myristoleate was similar to control values. It is suggested that stimulation of lipolysis in maternal tissues increases supply of free fatty acids to foetal blood and promotes the accumulation fatty acids and their esters in some foetal vascular walls.     

PKCδ knockdown inhibits free fatty acid induction of endothelial cell apoptosis

The mechanisms whereby free fatty acids induce endothelial cell apoptosis are not yet understood. The present study aimed to investigate the role of PKCδ in free fatty acid–induced endothelial cell apoptosis. In addition, we looked for evidence of apoptosis‐related interactions between PKCδ and Fas signal pathway. Human umbilical vein endothelial cells were treated with various concentrations of free fatty acids and transiently transfected with PKCδ siRNA or Fas siRNA to inhibit PKCδ or Fas expression. Cell proliferation was determined through colorimetric assays, and apoptosis was quantified using flow cytometry. Protein expression was determined from cell lysates using Western blots with antibodies against p‐PKCδTyr512, PKCδ, and Fas. Statistical analyses were performed. Free fatty acids had multiple effects on human umbilical vein endothelial cells, including concentration‐dependent inhibition of cell proliferation, induction of apoptosis, increased Fas expression, and increased PKCδ expression and phosphorylation. Inhibition of PKCδ mRNA expression by PKCδ siRNA led to a reduction in both free fatty acid–induced apoptosis and Fas expression. However, Fas siRNA treatment inhibited Fas, but not PKCδ, expression in human umbilical vein endothelial cells. The free fatty acid–induced apoptosis in endothelial cells are possibly mediated by PKCδ and may involve upregulation of its downstream Fas. Copyright © 2012 John Wiley & Sons, Ltd.     

Influence of a maternal cholesterol-enriched diet on [1-14C]-linoleic acid and L-[4, 5-3H]-leucine entry in plasma of rabbit offspring

Fetal development requires an important entry of essential free fatty acids (EFFA) and essential amino acids (EAA) into the fetal circulation. We have reported that a 0.2% enriched-cholesterol diet (ECD) during rabbit gestation significantly reduces fetus weight compared to control diet. It is known that dietary linoleic acid deficiency, an EFFA, during the fetal development induces an important impair to the somatic development. Moreover, intrauterine growth retardation induced a reduction of the flux of leucine, an EAA, from maternal to fetal circulation. Therefore, we hypothesized that the administration of an ECD induces modifications of placental lipid composition concomitant alterations of the transfer of linoleic acid and leucine in fetal circulation. Quantification of placental lipids revealed that in the ECD group a reduction of total-cholesterol (TC) and free-cholesterol (FC) is observed, however an increased in FFA and phospholipids is noticed when compared to the control group. In placenta from the ECD group, the FC/ TC ratio is significantly reduced compared to the control group. In the ECD group, the liver shows an increase of TC, FC and FFA compared to the control group. However, the quantity of triacylglycerol present in the liver from the ECD is significantly reduced compared to the control group. To evaluate the placental transfer of some essential nutrients, intravenous injection of [1-14C]-linoleic acid or L-[4, 5-3H]-leucine to term rabbit (control and ECD group) were done. Two hours later, rabbits were euthanized and we collected placenta, livers and blood from dams and offspring. The concentrations of both radiolabeled molecules (linoleic acid and its esterified form or leucine) were higher in the plasma of ECD offspring than those found in offspring from control diet. Despite such alteration of placental lipid composition, linoleic acid and leucine transfer by the placenta was not compromised but rather increased.     

Synthesis, turnover and compartment analysis of the free fatty acids in the placenta of rats.

The in vivo tracer method and in vitro acetate incorporation experiments were used to investigate the metabolism of placental free fatty acids. Analysis of data revealed that free fatty acids pass into the fetus from maternal plasma through a small placental compartment, which accounts for only 5 percent of all of the placental free fatty acids. The turnover time of this compartment is 0.57 min. The rate of placental fatty acid synthesis evaluated by both methods is very small and amounts to 0.003 mumols fatty acids/min/all placentas of one litter.     

Uterine uptake of amino acids and placental glutamine--glutamate balance in the pregnant ewe

The uterine uptake of amino acids was studied in 10 pregnant sheep with gestational ages of 114-146 days. After recovery from surgery, arterial and uterine venous samples were drawn simultaneously via indwelling catheters and analysed for amino acid and oxygen content. In seven ewes, amino acid concentrations were measured by a chromatographic technique. In four ewes, glutamate and glutamine arterio-venous differences across the uterine and umbilical circulations were measured by an enzymatic method. The uptake of neutral and basic amino acids was 66 mumol/mmol O2 and 17.3 mumol/mmol O2, respectively. Comparison of uterine and umbilical uptake shows that the bulk of the neutral and basic amino acids taken up by the pregnant uterus are transferred to the fetus. there was no significant uptake of acidic amino acids (i.e. glutamate, aspartate and taurine). glutamate was delivered from the fetus to the placenta but excretion of glutamate into the uterine circulation was negligible. Glutamine and asparagine were delivered to the fetus in amount which were two to three times larger than the placental uptake of glutamate and aspartate. Therefore placental conversion of exogenous glutamate and aspartate to glutamine and asparagine cannot account entirely for the fetal uptake of these amino acids.