Amino Acid Transport Systems β and A in Fetal T Lymphocytes in Intrauterine Growth Restriction and With Tumor Necrosis Factor-α Treatment

Abstract

Intrauterine growth restriction (IUGR) is associated with reduced activity of placental amino acid transport systems ␤ and A. Whether this phenotype is maintained in fetal cells outside the placenta is unknown. In IUGR, cord blood tumor necrosis factor (TNF)-␣ concentrations are raised, potentially influencing amino acid transport in fetal cells. We used fetal T lymphocytes as a model to study systems ␤ and A amino acid transporters in IUGR compared with normal pregnancy. We also studied the effect of TNF-␣ on amino acid transporter activity. In fetal lymphocytes from IUGR pregnancies, taurine transporter mRNA expression encoding system ␤ transporter was reduced, but there was no change in system ␤ activity. No significant differences were observed in system A mRNA expression (encoding SNAT1 and SNAT2) or system A activity between the two groups. After 24 or 48 h TNF-␣ treatment, fetal T lymphocytes from normal pregnancies showed no significant change in system A or system ␤ activity, although cell viability was compromised. This study represents the first characterization of amino acid transport in a fetal cell outside the placenta in IUGR. We conclude that the reduced amino acid transporter activity found in placenta in IUGR is not a feature of all fetal cells. (Pediatr Res 65: 51-56, 2009) I ntrauterine growth restriction (IUGR) occurs when a fetus fails to achieve its expected growth potential and may complicate approximately 5% of pregnancies (1). The shortand long-term consequences include perinatal morbidity with an increased risk of a "cerebral insult" and neurodevelopmental impairments in later childhood (2). In IUGR, there is a reduction in cord plasma concentration of amino acids including essential amino acids (3,4), underscored by a reduced activity of certain amino acid transport systems in the syncytiotrophoblast of human placenta (5).Amino acid transfer across the placenta is mediated by transporters in the maternal-facing microvillous plasma membrane (MVM) and fetal-facing basal plasma membrane (BM) of the syncytiotrophoblast (6). Plasma amino acid concentrations are higher in the fetus than in the mother, in keeping with active transport systems in MVM and BM. In IUGR, the activities of a range of amino acid transporters in MVM and BM are reduced (5). These include system A transporter in MVM (7-9), system L transporter in MVM and BM (10), system y ϩ L transporter in BM (10), and system ␤ transporter in MVM (11). Furthermore, stable isotope studies have shown that placental supply of leucine and phenylalanine exceeds fetal demand for protein synthesis by only a small amount suggesting a narrow safety margin for placental transfer of these essential amino acids (12). Thus, reduced amino acid placental transfer in IUGR has the potential to directly limit fetal growth (5,13).The basis for this decreased placental amino acid transport activity is not clearly understood. It may have a genetic basis or may be secondary to an alteration in the metabolic and/or endocrine milieu of the mother ...

Amino-acid transporters in T-cell activation and differentiation

“…For example, fetal T cells express SNAT-1 and SNAT-2 mRNAs. 15 T cells express various numbers of the system BETA family, including GAT-1, 9 , 16 , 17 GAT-2, 17 BGT1 18 and TAUT. 19 Other AA transporters have also been reported in T cells, such as ASCT2, 10 LAT1 20 and Cat-1.…”

Maternal protein intake during pregnancy and linear growth in the offspring

“…Includes 1537 mother-child pairs. by intrauterine growth restriction are characterized by reductions in both cord plasma amino acid concentrations and placental amino acid transporter activity (42,43). Although reduced amino acid availability to the fetus can result from inadequate maternal concentrations, placental transport and umbilical uptake of certain amino acids may also be impaired by high maternal concentrations because of competition for transporters (43).…”

Melatonin Supplementation Alters Maternal and Fetal Amino Acid Concentrations and Placental Nutrient Transporters in a Nutrient Restriction Bovine Model

“…Amino acid concentrations are greater in amnion and allantois fluids than in maternal blood in humans and livestock, indicating increased transport across the placenta [12]. In humans and in pig models of compromised pregnancies, amino acid transport across the placenta is decreased resulting in poor fetal growth [13,14]. In a maternal nutrient restriction sheep model, placentomes from IUGR pregnancies had decreased cationic and neutral amino acid transporters [6].…”

“…Supplementation with amino acids that have angiogenic and vasodilative properties have improved uterine blood flow and fetal growth in humans, pigs, sheep, and mice [12]. Evaluation of amino acid transport systems in compromised pregnancies has been characterized in humans [14,15] sheep, and rats [13,16] while characterization of transport systems in bovines is limited [7]. Increased placental transporter density is necessary to facilitate increased amino acid demand during the last third of pregnancy, which is vital for fetal growth and development, as well as postnatal health and growth.…”