248 Maternal Nutrient Restriction During Mid-gestation Decreases Uteroplacental Release and Fetal Uptake of Essential Amino Acids in Sheep

To examine the effects of maternal nutrient restriction on net uteroplacental flux during mid-gestation, 14 singleton ewes (48.2 ± 4.0 kg body weight) were fed 100% (control; CON; n = 7) or 60% of nutrient requirements (restricted; RES; n = 7) from day 50–90 (mid-gestation). On day 90, uteroplacental blood flow was measured via Doppler ultrasonography and blood samples were collected from the femoral artery, uterine vein, umbilical artery, and umbilical vein. Blood vessel glucose and amino acids (AA) concentrations were measured and arterial-venous (uterine, AV; fetal, va) differences and net fluxes were calculated. Data were analyzed using the GLM procedure of SAS for effects of treatment. Nutrient restriction during mid-gestation did not influence (P ≥ 0.17) uterine or umbilical blood flows. Uterine AV and fetal va differences of total, essential, and nonessential AA were not influenced (P > 0.10) by nutrient restriction. Nutrient restriction decreased (P ≤ 0.05) uterine and uteroplacental release of total AA and tended to decrease (P = 0.07) total AA uptake by the fetus. Uteroplacental release and fetal uptake of essential AA were decreased (P = 0.03) with RES by 53.4% and 45%, respectively. Uterine and uteroplacental release of nonessential AA were decreased (P = 0.03) with RES but, fetal uptake was not affected (P = 0.14). Nutrient restriction decreased (P ≤ 0.04) fetal uptake of methionine, phenylalanine, threonine, and valine and tended to decrease (P ≤ 0.10) fetal uptake of isoleucine, leucine, and tryptophan. Umbilical artery glucose concentrations were 32% lesser (P = 0.01) with RES and RES tended to increase (P = 0.08) fetal glucose uptake. Nutrient restriction during mid-gestation altered uteroplacental and fetal flux of AA in the current study. The results may indicate that fetal metabolism shifts to adapt to reduced AA supply which results in greater glucose utilization.

Ovine uteroplacental and fetal metabolism during and after fetal cortisol overexposure in late gestation

Cortisol modifies fetal metabolism in preparation for delivery, but whether preterm cortisol exposure programs persisting changes in fetoplacental metabolism remains unknown. This study infused fetal sheep with saline ( n = 36) or cortisol ( n = 27) to raise fetal plasma cortisol to normal prepartum concentrations for 5 days from day 125 of gestation (term: ≈145 days). Fetal uptake and uteroplacental metabolism of glucose, oxygen, and lactate, together with fetal hepatic glucogenic capacity, were measured on the final day of infusion or 5 days later. Cortisol reduced adrenal weight and umbilical glucose uptake during infusion but increased fetal glucose concentrations, hepatic glycogen content, and hepatic glucogenic enzyme activity (fructose-1,6-bisphosphatase and glucose-6-phosphatase) and gene expression ( PC and G6PC) compared with saline infusion. Postcortisol infusion, umbilical glucose uptake, and hepatic glucose-6-phosphatase activity remained low and high, respectively, whereas fetal glucose levels normalized and hepatic glycogen was lower with higher adrenal weights than in controls. Cortisol infusion increased the proportion of total uterine glucose uptake consumed by the uteroplacental tissues, irrespective of age. Placental tracer glucose transport capacity was also increased after, but not during, cortisol infusion, without changes in placental glucose transporter gene expression. Blood lactate concentration and Pco2 were higher, whereas pH and O2 content were lower in cortisol-infused than saline-infused fetuses, although uteroplacental metabolism and fetal uptake of oxygen and lactate were unaltered. The results suggest that preterm cortisol overexposure alters fetoplacental metabolism and adrenal function subsequently with persisting increases in uteroplacental glucose consumption at the expense of the fetal supply.

Relationship of fetal alanine uptake and placental alanine metabolism to maternal plasma alanine concentration

Uterine and umbilical uptakes of alanine (Ala) were measured in 10 ewes before (control) and during intravenous infusion of Ala, which increased maternal arterial Ala concentration from 115 ± 14 to 629 ± 78 μM ( P < 0.001). In 8 of these ewes, placental Ala fluxes were traced by constant intravenous infusion ofl-[3,3,3-2H3]Ala in the mother andl-[1-13C]Ala in the fetus. Rates are reported as micromoles per minute per kilogram fetus. Ala infusion increased uterine uptake (2.5 ± 0.6 to 15.6 ± 3.1, P < 0.001), umbilical uptake (3.1 ± 0.5 to 6.9 ± 0.8, P < 0.001), and net uteroplacental utilization (−0.7 ± 0.8 to 8.6 ± 2.7, P < 0.01) of Ala. Control Ala flux to fetus from mother ( R f,m) was much less than the Ala flux to fetus from placenta ( R f,p) (0.17 ± 0.04 vs. 5.0 ± 0.6). Two additional studies utilizingl-[U-13C]Ala as the maternal tracer confirmed the small relative contribution of R f,m to R f,p. During maternal Ala infusion, R f,m increased significantly ( P < 0.02) but remained a small fraction of R f,p (0.71 ± 0.2 vs. 7.3 ± 1.3). We conclude that maternal Ala entering the placenta is metabolized and exchanged for placental Ala, so that most of the Ala delivered to the fetus is produced within the placenta. An increase in maternal Ala concentration increases placental Ala utilization and the fetal uptake of both maternal and placental Ala.

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).