Fetal Uptake Research Articles

Whole-body retention and fetal uptake of 65Zn in pregnant mice fed a Zn-deficient diet.

Whole-body retention and fetal uptake of 65Zn under a Zn-deficient diet were studied in pregnant mice in the late gestational stage after a single oral administration of 65Zn. Whole-body retentions were much greater in mice given a Zn-deficient diet than in those given a Zn-normal diet. Accordingly, the amount of 65Zn transmitted to the offspring in utero was greater in the Zn-deficient diet group. In another experiment, fetal uptake of 65Zn in dams on gestation day 17 was examined over a period of 24 hr after a single intravenous administration of 65Zn to the Zn-deficient and Zn-normal animals. There was no major difference in fetal uptake between the two groups, indicative that approximately a similar proportion of the 65Zn retained in the maternal body was transmitted to the in utero offspring in both groups.

Similar properties of fetal and adult amine transporters in the rat brain

A variety of drug classes, including psychomotor stimulants and antidepressants, interact with monoamine transporters in order to exert their effects. Although these transporters have been extensively characterized in the adult brain, little is known about uptake mechanisms in the fetal system. High affinity dopamine (DA) and serotonin (5-HT) uptake in the striatum and frontal cortex, respectively, were examined in rat fetuses (embryonic day 20; E-20). These results were then compared to uptake in adult rat synaptosomal preparations of the same regions. The data indicate that the fetal (E-20) uptake mechanism is sodium-dependent. Furthermore, the potency of various agents to inhibit transporter function was assessed. These drugs produced a concentration-dependent inhibition of uptake, and the resulting IC 50 values were not significantly different from those obtained in the adult preparations. Our results provide evidence that the affinity of monoamine uptake inhibitors for fetal (E-20) DA and 5-HT transporters is similar to that observed with adult transporters. This observation has broad implications when considering neuronal development and in utero exposure to drugs that exert their effects through these transporters.

Amino acid uptake by the fetal ovine hindlimb under normal and euglycemic hyperinsulinemic states

As part of an effort to establish the contribution of different fetal organs to fetal amino acid metabolism, we measured in nine sheep fetuses the uptake of 27 amino acids by the hindlimb under normal conditions and conditions by euglycemic hyperinsulinemia. The fetal hindlimb is representative of nonvisceral tissues, which in the mature fetus account for approximately 70% of fetal weight and 30% of fetal O2 consumption. In the normal condition, there was a significant uptake of 21 amino acids for a net total nitrogen uptake of 132 +/- 21 mg N.day-1 x 100 g-1. The amino acids taken up by the fetal limb included alanine and glutamine. In addition, the fetal limb had significant glutamate and serine uptakes. Because glutamate flows from fetus to placenta and there is no fetal uptake of maternal serine, this indicates production and interorgan transport of these amino acids within the fetus. Insulin infusion significantly decreased the arterial concentration of every amino acid with the exception of cystathionine and significantly increased limb blood flow and glucose uptake. It significantly increased the limb uptake of alanine, asparagine, glycine, isoleucine, methionine, and tyrosine, decreased the uptake of aspartate, and produced no significant change in the net total nitrogen uptake, which remained similar to control (137 +/- 16 mg N.day-1 x 100 g-1).

Glutamine carbon disposal and net glutamine uptake in fetuses of fed and fasted ewes.

We have traced ovine fetal glutamine carbon uptake and disposal in 7 chronically catheterized fetuses of fed ewes and 10 fetuses of 48-h fasted ewes. Net fetal glutamine uptake (Fick principle, antipyrine blood flow) was 10.0 +/- 2.0 mumol.kg-1 x min-1 in fed fetuses and 6.4 +/- 1.4 mumol.kg-1 x min-1 in fasted fetuses [not significant (NS)]. However, net fetal glutamine uptake was linearly related to the umbilical vein glutamine level (P < 0.05) in fed and fasted fetuses. In contrast, fetal glutamate transfer to the placenta was 4.0 +/- 0.8 mumol.kg-1.min-1 in the fed state and 2.7 +/- 0.1 mumol.kg-1 x min-1 in the fasted state. Net fetal glutamine uptake and fetal glutamate transfer to the placenta were directly correlated (P < 0.05). Fetal glutamine carbon disposal was measured using a primed continuous infusion of [U-14C]-glutamine over a 3-h period and blood sampling during the last hour of infusion (steady state). Disposal was 20.9 +/- 2.6 mumol.kg-1 x min-1 in the fed state and 18.6 +/- 2.3 mumol.kg-1 x min-1 in the maternal fasted state (NS). Glutamine carbon disposal did not correlate with fetal arterial glutamine levels and was not influenced by maternal nutritional state.

Effect of maternal diabetes on the expression of genes regulating fetal brain glucose uptake

Effect of maternal diabetes on the expression of genes regulating fetal brain glucose uptake

Protein turnover in the human fetus studied at term using stable isotope tracer amino acids

Before elective cesarean delivery (4 h), we infused L-[1-13C]leucine and L-[15N]phenylalanine into the maternal circulation and measured enrichment and concentration of amino acids and carbon dioxide in cord blood of six normal human fetuses at delivery. There were net fetal uptakes of leucine (2.22 +/- 0.29 mumol.kg-1.min-1) and phenylalanine (0.80 +/- 0.11 mumol.kg-1.min-1) with net outputs of CO2 (6.11 +/- 1.12 ml.kg-1.min-1) and the transamination product of leucine, alpha-ketoisocaproate (1.04 +/- 0.32 mumol.kg-1.min-1). Fetal amino acid oxidation accounted for a substantial proportion of the flux from the mother (leucine, 0.36 +/- 0.09 mumol.kg-1.min-1 and phenylalanine, 0.18 +/- 0.04 mumol.kg-1.min-1). Fetal whole body accretion of leucine carbon (0.82 +/- 0.21 mumol.kg-1.min-1) was 69% of the umbilical uptake, and that of phenylalanine (0.62 +/- 0.08 mumol.kg-1.min-1) was 78%. Fetal whole body protein synthesis was approximately 13 g.kg-1.day-1, i.e., much faster than in adults but similar to that in the newborn. Net protein accretion was 2-4 g.kg-1.day-1. The placental supply of leucine and phenylalanine exceeds the fetal demand for protein synthesis by only a small amount, suggesting that the safety margin of placental transfer may be small for these amino acids. The results suggest that the method could be applied safely to studies of fetal growth retardation.

Embryo-Fetal Development Influenced by Lead Exposure in Iron-Deficient Rats

Lead administered (250, 500, 1000 and 2000 ppm Pb as lead nitrate) through drinking water from the 6th to the 14th day of gestation in iron-deficient rats, resulted in a significantly reduced litter size, reduced fetal weight and a reduced crown-rump length, increased resorption and a higher blood-lead uptake in those groups receiving 1000 and 2000 ppm Pb. These animals also had a higher placental lead uptake. However, the level was the same in both groups. Fetal lead uptake remained the same whether or not 2000 ppm lead was given to an iron-deficient or normal iron groups of mothers. This indicates that iron-deficiency renders female rats more susceptible to inducing embryo- and feto-toxicity when given lead through their drinking water.

Plasma total and free concentrations of bupivacaine and lignocaine in mother and fetus following epidural administration, singly or together

Forty six women undergoing elective caesarean section under epidural blockade were given 20 ml of either bupivacaine 0.5% plain (B) or with adrenaline 5 μg/ml (B + A), lignocaine 2% with adrenaline 5 μg/ml (L + A) or a mixture of equal parts of L + A and B + A (BLA). Further doses of the same solution were given at 20 min if necessary. Free and total plasma concentrations of the local anaesthetics were measured in maternal venous plasma 10, 20, 40, 60 and 120 min after the main dose and in umbilical venous plasma at delivery. Protein binding of both drugs was significantly higher in mother than baby. Lignocaine did not affect bupivacaine binding but lignocaine binding was higher in group BLA than L + A. Otherwise the presence of one drug had little effect on the disposition of the other drug in mother or baby. No plasma concentrations were considered toxic. Adrenaline did not reduce maternal C max of free bupivacaine and appeared to be associated with increased fetal uptake of bupivacaine.

Uterine and umbilical blood flows and net nutrient uptake by fetuses and uteroplacental tissues of cows gravid with either single or twin fetuses.

To evaluate the influence of cow breed and number of fetuses on uterine and umbilical blood flows and nutrient fluxes or uterine tissues from gravid cows, surgery was performed on Charolais or Hereford cows with single or twin fetuses at 177 +/- .2 d (mean +/- SEM) after mating. Indwelling catheters were placed in a fetal femoral artery and vein, in an umbilical vein of each fetus, and in a uterine artery and vein of each gravid horn. Deuterium oxide (D2O) was infused into a fetal femoral vein at 183 +/- .3 and 190 +/- .5 d after mating to estimate uterine and umbilical blood flows (liters/minute). Blood oxygen and plasma glucose and lactate concentrations were determined and uterine arterio-venous (A-V) and umbilical venous-fetal arterial (v-a) differences and net uterine and fetal uptakes were calculated. Net utilization by the uteroplacenta was calculated as the difference between uterine and fetal net uptakes. Uterine blood flows were lower (P less than .01) in Hereford (4.80 +/- .28) than in Charolais (7.07 +/- .33) and lower (P less than .01) per fetus in cows with twin fetuses (5.22 +/- .34) than in cows with a single (6.65 +/- .28) fetus. Umbilical blood flows were greater for single than for twin fetuses. Fetal oxygen and glucose net uptakes averaged 57 and 12%, respectively, of net uteroplacental utilization. Lactate was released from uteroplacental tissues to fetal (42%) and maternal circulations (58%). Fetal oxygen uptakes tended to be less for twin fetuses (P = .08) than for a single fetus.(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal heart rate variability and cerebral oxygen consumption in fetal sheep during asphyxia

This study was designed to examine the relationship between fetal heart rate variability and fetal cerebral oxygen uptake. Fetal sheep were chronically prepared with catheters and electrodes to determine cerebral blood flow (microsphere method), cerebral arteriovenous oxygen difference, and the electrocardiogram. An adjustable occluder was placed on the maternal common internal iliac artery to induce fetal asphyxia by reducing uterine blood flow. Fetal heart rate variability tended to decrease in the first 11 min of asphyxia, when cerebral oxygen consumption was approximately 53% of control. Despite stable cerebral oxygen consumption and worsening metabolic acidosis, however, fetal heart rate variability progressively returned towards normal by 36 min. There was no relationship between the depression of FHR variability and the degree of reduction of cerebral oxygen consumption. Nor was there any relationship between an alteration in regional cerebral blood flow or myocardial blood flow and the return of FHR variability with increasing duration of asphyxia. We conclude that there is an association between loss of fetal heart rate variability and reduced cerebral oxygen consumption, but the reduced variability does not persist with time at this degree of reduced cerebral metabolism in fetal sheep. This appears to be at variance with human clinical experience. Among the explanations for this may be insufficiently severe asphyxia, a species difference, removal of an inhibitor to FHR variability, or progressive use of other substrates for metabolism.

Effects of Glucose Infusion on Leucine Transamination and Oxidation in the Ovine Fetus

During fasting of the ewe, the rate of amino acid oxidation by the ovine fetus increases substantially. We hypothesized that the increase in amino acid oxidation derived mainly from reduced protein synthesis. We further hypothesized that fetal glucose supplementation would result in diminished amino acid oxidation. To test these hypotheses, nine ovine fetuses were infused with [15N,1-13C]leucine to determine the rates of leucine appearance and disposal. Simultaneously, the fetal uptake of leucine was determined. Animals were studied in the fed and fasted state. After baseline measurements, glucose was infused into the fetal inferior vena cava at a rate estimated to match the fetal glucose uptake. Results of these studies indicate that leucine nitrogen flux, leucine carbon flux and fetal leucine uptake were constant. Leucine oxidation was increased by 50% in the fasted state (6.3 versus 13.4 mumol/min); glucose infusion resulted in a 25% decline in oxidation (to 10.4 mumol/min) in the fasted state, but had no effect in the fed state. Mean leucine umbilical uptake during fasting was 9.3 mumol/min, 4.1 mumol/min less than leucine oxidation. These data suggest that leucine (and potentially other amino acids) may be in negative balance during maternal fasting, and can be spared by supplementation of the fetus with exogenous glucose.

Maternal and fetal influences on uterine and conceptus development in the cow: II. Blood flow and nutrient flux

Objectives of this study were to evaluate maternal and fetal influences on uterine and umbilical blood flows and nutrient fluxes of gravid uterine tissues of cows. Brahman cows with Brahman or Charolais fetuses and Charolais cows with Brahman or Charolais fetuses were used. Indwelling catheters were placed into a uterine artery and vein, an umbilical vein, and a fetal femoral artery and vein at 220 +/- .4 d after mating. Uterine and umbilical blood flows (liters/min) and net uptakes of oxygen, glucose, lactate, alpha-amino N, urea N, ammonia N, and estrone sulfate by the gravid uterus, fetus, and uteroplacenta were determined on d 227 +/- .4. Uterine blood flows in Brahman cows with Brahman (5.01) or Charolais (4.66) fetuses were similar but less (P less than .001) than in Charolais cows with Brahman (7.14) or Charolais fetuses (9.24), which differed (P less than .01). Umbilical blood flows of Charolais (3.78) were greater (P less than .01) than those of Brahman (2.29) fetuses. Rate of placental D2O clearance as well as net fetal uptake of oxygen, glucose, and alpha-amino N, gravid uterine uptake of alpha-amino N, and uteroplacental uptake of glucose and release of estrone sulfate were greater with Charolais than with Brahman fetuses. Gravid uterine oxygen uptake and estrone sulfate release and gravid uterine and uteroplacental lactate output were influenced by the interaction between cow and fetal breed. It is suggested that fetal growth may be limited by uterine blood flow and by function of the uteroplacenta, particularly in late gestation.

Effect of occluding one umbilical artery on placental oxygen transport

Placental O2 transport was studied in seven fetal lambs before and after occluding one of the two umbilical arteries. Ethanol was used to measure uterine and umbilical blood flows using the steady-state transplacental diffusion method. Blood samples were drawn from umbilical artery, umbilical vein, both uterine veins, and maternal artery and analyzed for blood flow indicator, O2 content, PO2, PCO2, and pH. Occlusion reduced the placental mass and the uterine blood flow, which was available for transplacental exchange, to 49.5 and 46.5% of control, respectively. After occlusion, fetal blood pressure increased 38%, total umbilical blood flow decreased 25%, total fetal O2 uptake decreased 26%, fetal blood flow to the unoccluded placenta increased 52%, and the O2 flux from unoccluded placenta to fetus increased 49%. This increased flux was accompanied by a decrease in the PO2 of maternal venous blood from the unoccluded placenta and an enlargement of the transplacental PO2 gradient, resulting in a marked drop in umbilical venous PO2 (28.3 to 17.7 Torr). This evidence supports the hypothesis that placental O2 diffusing capacity is a limiting factor in placental O2 transport and agrees with other studies indicating the absence of homeostatic mechanisms for preventing acute changes of PO2 in the placental circulation.

Uterine Blood Flow, Oxygen and Glucose Uptakes at Mid-Gestation in the Sheep

In early ovine fetal development, the placenta grows more rapidly than the fetus so that at mid-gestation the aggregate weight of placental cotyledons exceeds fetal weight. The purpose of this study was to compare two separate methods of measuring uterine blood flow and glucose and oxygen uptakes in seven mid-gestation ewes, each carrying a single fetus. Uterine blood flow to both uterine horns was measured by microsphere and by tritiated water steady-state diffusion methodology. Calculations of tritiated water blood flows and oxygen and glucose uptakes were based on measurements of arteriovenous concentration differences across each uterine horn. The distribution of blood flow and oxygen uptake between the two uterine horns was strongly correlated with placental mass distribution. The two methods gave comparable results for uterine blood flow (457 +/- 35 vs 476 +/- 35 ml/min), oxygen uptake (457 +/- 35 vs 476 +/- 35 mumol/min), and glucose uptake (63 +/- 8 vs 64 +/- 6 mumol/min). Uterine blood flow was approximately 38% of the late gestation value and 56.1 +/- 1 times higher than umbilical blood flow. Uteroplacental oxygen consumption was about 58% of late gestation measurements and 3.9 +/- 0.5 times higher than fetal oxygen uptake. We confirm that the large placental mass of mid-gestation is associated with high levels of maternal placental blood flow and placental oxidative metabolism.

Foetal and Maternal Distribution of Inhaled Mercury Vapour in Pregnant Mice: Influence of Selenite and Dithiocarbamates

The distribution of mercury after inhalation of metallic mercury vapour (6-8 mumols 203Hg0/kg b.wt.) was studied in pregnant mice (day 17 of gestation) after pretreatment with selenite (10 mumols Se/kg b.wt. intraperitoneally 1 hr before inhalation), thiram, disulfiram or diethyldithiocarbamate (1 mmol/kg orally 2 hr before inhalation of Hg0). For comparison, the effects of thiram, disulfiram and diethyldithiocarbamate on the distribution of mercury after administration of ionic mercury (7 mumols 203HgCl2/kg b.wt. intravenously) were also studied. Selenite pretreatment caused a longer retention of mercury in maternal tissues but decreased the foetal concentrations after 203Hg0 inhalation, similarly to what has been shown previously after administration of ionic mercury (Hg2+). Pretreatment with the three dithiocarbamates markedly increased the uptake in maternal brain and fat and decreased the foetal concentrations after intravenous injection of 203HgCl2. In contrast, no change in foetal uptake and only slight changes in maternal tissue concentration of mercury were observed after treatment with the dithiocarbamates followed by inhalation of 203Hg0, compared with 203Hg0 inhalation alone. The results are in favour of a firmer binding of mercury after Hg0 inhalation, when oxidation of Hg0 to Hg2+ occurs intracellularly, than after Hg2+ injection. Further studies, using repeatedly low dose administration of selenium, are needed to draw any conclusions concerning the protective effects of selenium after exposure to metallic mercury vapour.

Placental Transfer of Glucose and Amino Acids in Intrauterine Growth Retardation: Studies with Substrate Analogs in the Awake Guinea Pig

After experimentally inducing growth retardation by unilateral uterine artery ligation in midpregnancy, placental blood flow (PBF) (microsphere technique) and placental transfer of 14C-aminoisobutyric acid (AIB) and 3H-methylglucose (MG) were studied at d 44, 50, or 63 of gestation in 19 chronically catheterized awake guinea pigs. At d 44, fetal wt (FW) and placental wt were reduced by 16 and 18%, respectively, in the ligated horn and FW/PBF was increased by 122%. Placental efficiency to transfer MG and AIB (fetal dpm/g placenta) was maintained in the ligated horn, feto-placental extraction (feto-placental dpm/PBF) was increased, and placental transfer of the substrate analogs (fetal dpm/g fetus) was unchanged. At d 50 and 63, placental wt and FW were reduced in proportion (approximately 40%) in the growth-retarded group and FW/PBF was increased by 80 and 51%, respectively. Placental transfer of AIB was reduced by 33% at d 50 and by 18% at d 63. In addition, placental efficiency to transfer AIB was reduced by 36% at d 50 and by 22% at d 63 in the growth-retarded group. Fetal uptake of MG per g fetus was slightly reduced (-6%) at d 50 of gestation, but unaffected at d 63. Extraction of MG from the maternal PBF was increased, whereas the wt-specific transfer capacity of the placenta was unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative embryotoxicity of selenite and selenate: uptake in murine embryonal and fetal tissues and effects on blastocysts and embryonic cells in vitro

The placental transfer and distribution pattern of selenium (Se) in embryonic and fetal tissues after intravenous injection of Na 2 75SeO 3 (Se 4+) or Na 2 75SeO 4 (Se 6+) has been investigated in mice in early, mid, and late pregnancy by use of whole-body autoradiography combined with gamma-counting. The given doses correspond to 45 μg Se/kg. In order to compare the direct toxicity in early embryonic stages, the two valence forms were studied by using in vitro systems with (1) mouse blastocysts and (2) chick embryo fibrobaasts, differentiating into chondrocytes. The embryonic and fetal uptake after administration of Se 4+ and Se 6+ was almost identical. The placental transfer of Se was restricted but, nevertheless, increased with time after dosing and with progression from embryonic through fetal stages thereby suggesting active placental transfer. The highest uptake in the embryo was observed in the neuro-epithelium while the eye, liver and skeleton dominated the distribution pattern in the fetal period. Selenite (Se 4+) was more toxic than selenate (Se 6+) in the vn vitro system, in which embryonic mesenchymal limb bud cells differentiated into chondrocytes as well as in the blastocyst culture system. The results may suggest a direct effect of Se in the embryo as explanation to reported malformations in experimental studies.

Uptake and Distribution of Lidocaine in Fetal Lambs

The fetal uptake of lidocaine was measured continually and quantitatively during and after a constant rate intravenous (iv) maternal infusion into five chronically prepared pregnant ewes. Lidocaine, 6 mg/kg (base), was infused at a constant rate for 1 h and measurements continued to 5 h. Rate of fetal uptake was determined from the product of the umbilical venous (UV) and fetal aortic (FA) concentration difference and umbilical blood flow (Qu). Total fetal uptake was determined by integrating fetal uptake rate with respect to time. Maternal and fetal protein binding was determined, and its effect on fetal blood concentrations was evaluated. Mean total fetal uptake as it related to time and infused dose increased linearly (r = 0.998, P less than 0.001) with a constant, weight-normalized fetal-maternal dose fraction of 0.45 during the infusion. Despite rapidly declining blood concentrations after the infusion, uptake increased an additional 17%. The sevenfold variation in uptake appeared to be inversely related to the biodegradation rate of lidocaine. Fetal-maternal concentration ratios (F/M) increased during declining blood concentrations. Protein binding determinations for maternal and fetal blood were 43.6 +/- 2.48% and 26.9 +/- 1.59%, respectively. These values were used to calculate the F/M in conjunction with the maternal and fetal pH. At maternal-fetal equilibrium the calculated F/M, 1.0 +/- 0.05, closely approximated the observed, 1.0 +/- 0.03. Variations in lidocaine concentrations among the vital organs 4 h after the infusion were small, but high concentrations of metabolites were found in the lungs and kidneys. The results challenge the validity of placental transfer estimates commonly based on the F/M and umbilical cord blood concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution of Free Amino Acids in Streptozotocin-Induced Diabetic Pregnant Rats, Their Placentae and Fetuses

Amino acid levels in the non-pregnant streptozotocin (STZ)-induced diabetic rat have been shown to be abnormal. Our preliminary studies showed that placental transport, fetal serum levels and tissue uptake of the non-metabolizable amino acid alpha-amino isobutyric acid (AIB) were decreased in STZ-diabetic pregnant rats. In the present experiments, amino acid concentrations were measured in maternal (MS) and fetal (FS) sera and placentae (PL) by high performance liquid chromatography (HPLC) after triple extraction in 80% ethanol. Control (C), STZ-diabetic (D) and insulin-treated diabetic (DI) animals were studied at 22 days gestation. Pregnant diabetic rats had low serum levels of Gln, Lys, and Ser and insulin treatment corrected Gln and Ser but not Lys levels. Branched-chain amino acids did not show the large elevation characteristic of the non-pregnant diabetic rat. Placental levels of Tau, Gln, HPr, Thr and Lys were depressed in the diabetic animals and insulin treatment only partially improved these amino acid profiles. Placental amino acid levels did not always reflect maternal serum levels. Serum levels of most amino acids were lower in the fetus of the diabetic rat than in the fetus of the control rat. The notable exception was Ala which was higher in the fetuses of the diabetic animals. Insulin treatment of the mother did not correct many of the fetal amino acid levels even though maternal and fetal serum glucose levels at the time of autopsy were normal. The ability to maintain normal serum levels of many amino acids is impaired in the fetus of the diabetic rat.(ABSTRACT TRUNCATED AT 250 WORDS)

UPTAKE OF AMINO ACIDS AND AMMONIA AT MID‐GESTATION BY THE FETAL LAMB

Fetal uptakes of amino acids and ammonia via the umbilical circulation were measured in single pregnant ewes at mid-gestation (range 66-81 days). There were significant net fluxes from placenta to fetus of ammonia and twelve amino acids (in decreasing order: glutamine, glycine, alanine, proline, lysine, arginine, threonine, valine, leucine, tyrosine, asparagine, isoleucine) and net fluxes from fetus to placenta of glutamate and serine. The estimated serine flux was 139 mumol day-1 (g fetal dry wt)-1. Comparison with late gestation data indicated a similar pattern of amino acid exchange. However, the relatively large placental uptake of fetal serine was a distinctive feature of mid-gestation. The net fetal uptake of amino acid nitrogen was 2.83 +/- 0.66 micrograms N (mumol O2 uptake)-1, or 18 mg N day-1 (g dry wt)-1. This uptake was similar in magnitude to the combined fetal requirements for nitrogen accretion and urea synthesis and represented approximately 32 and 43% of fetal carbon and energy requirements, respectively.