Preserved Fetal Plasma Amino Acid Concentrations in the Presence of Maternal Hypoaminoacidemia

Abstract

ABSTRACT. The effects on the conceptus of persistently decreased maternal plasma amino acid concentrations were studied in pregnant rats by the infusion of glucagon (0.21 mglday) to the mother from day 14 to 20 of gestation with a subcutaneous, osmotically driven minipump. Controls received diluent. The experimental animals either had normal caloric intake and weight gain, or diminished caloric intake with no weight gain. Both experimental groups exhibited a decrease in plasma total amino acid concentration of approximately 50%. Maternal plasma glucose and insulin concentrations were unaffected except for slight decreases in the low weight gain group. At cesarean section on day 20, fetal weight was unaffected in the normal weight gain group, while the low weight gain animals exhibited intrauterine growth retardation. Fetal plasma glucose and insulin concentrations were unaffected. Despite the marked decrease in maternal plasma total amino acid concentration, fetal plasma total amino acid concentration was unaffected. Individual plasma amino acid concentrations in the normal weight gain mothers and fetuses revealed a spectrum of changes. Some maternal amino acids were decreased by more than 60% (a-aminobutyric acid, asparagine, threonine, glutamine, alanine) while others were unaffected (tyrosine, tryptophan, phenylalanine, histidine). In general, amino acids that were decreased in the mother exhibited no change or a lesser decrease in fetal plasma concentration, while those that were unaffected in the mothers showed increased fetal concentrations. Fetuses from the low weight gain mothers had plasma amino acid ~rofiles that were similar to those of the normal weight gain mothers. We speculate that the preserved fetal amino acid concentrations are due to enhanced placental transport of amino acid secondary to maternal substrate decrease. (Pediatr Res 20: 1071-1076,1986 which are specific for each group of nutrients. In the case of amino acids it has been demonstrated that the placenta is capable of concentrating most amino acids intracellularly in order to achieve transport to the fetus against a concentration gradient (1-4). This results in fetal plasma amino acid concentrations which can be more than three times higher than maternal plasma concentrations (1, 5 , 6).Maternal substrate limitation, presumably by limiting nutrient transport to the fetus, can lead to IUGR. This has been demonstrated experimentally in models utilizing starvation (7) or ligation of the uterine artery (8). These manipulations result in nonspecific reduction in the delivery of substrates, including glucose and amino acids, such that the roles of specific substrates remain obscure.The aim of the present study was to develop a model in which maternal plasma amino acid concentrations are selectively reduced without significant changes in the maternal concentrations of other nutrients. In nonpregnant male rats, a persistent increase in glucagon has been shown to be associated with a decrease in total plasma amino acid concentrations (9). Thi...

1H-NMR-Based Metabolic Profiling of Maternal and Umbilical Cord Blood Indicates Altered Materno-Foetal Nutrient Exchange in Preterm Infants

“…Intriguingly, however, neither an enhanced level of ethanol nor any other evident change was seen in the arterial and venous umbilical cord plasma from this mother–infant pair. The same preservation in cord plasma amino acid concentrations was observed in the plasma from rat pups born from dams that had a severe diet-induced depletion of total plasmatic amino acids [33]. This finding is consistent with the previous study of venous umbilical cord plasma by 1 H NMR, wherein ethanol was identified in 5 venous umbilical cord plasma samples, suggesting ethanol to be endogenous.…”

Effects of Maternal Protein Malnutrition on Fetal Growth, Plasma Insulin-like Growth Factors, Insulin-like Growth Factor Binding Proteins, and Liver Insulin-like Growth Factor Gene Expression in the Rat

“…Davenport ML, D'Ercole AJ, Effect of maternal fasting on fetal control pups in our study. indicate enhanced placental transport Of amino acids such that i s , Thissen JP, Triest S, ~oats-staats BM, Underwood LE, Mauerhoff T, Maiter D, availability to the fetus is maintained (57). hi^ might partly…”

The Placenta: Not Just a Conduit for Maternal Fuels

“…This process can be blocked by inhibitors of protein synthesis, demonstrating that increase in transport capacity probably represents the synthesis of new transporter proteins (38). An in vivo study in rats demonstrated maintenance of fetal amino acid concentrations despite prolonged hypoaminoacidemia in the mother, suggesting that a similar process of amino acid transporter protein synthesis might occur in vivo in response to a decrease in circulating amino acid concentrations (39). These results take on added importance relative to observations by Cetin et al (40), who showed, from umbilical blood vessel-sampling data, that in humans the concentration of a-amino nitrogen was lower in maternal and fetal plasma in pregnancies complicated by fetal growth restriction.…”

“…In contrast, fetal O 2 consumption is relatively constant, indicating that a reciprocal relationship may exist, at least over the short term, between glucose oxidation and the oxidation of other energy-producing substrates. In fetal sheep, the leucine oxidation-disposal ratio increases during sustained glucose deficiency, hypoglycemia, and hypoinsulinemia (62), and in fetal rats, sustained hypoglycemia increases protein catabolism and limits fetal growth (39). Thus, at least some amino acids can be diverted from protein synthesis and net protein accretion to protein catabolism and oxidation, either directly or via gluconeogenesis.…”