Placental Transport of Leucine, Phenylalanine, Glycine, and Proline in Intrauterine Growth-Restricted Pregnancies

Abstract

L-[1-13C]Leucine, [1-13C]glycine, L-[1-13C]phenylalanine, and L-[1-13C]proline were infused as a bolus into the maternal circulation of seven appropriate for gestational age at 30.3 +/- 3.0 wk and 7 intrauterine growth-restricted pregnancies at 26.5 +/- 1.0 wk gestation to investigate placental transport in vivo. Umbilical venous samples were obtained at the time of in utero fetal blood sampling at 450 +/- 74 sec from the bolus injection. In normal pregnancies the fetal/maternal (F/M) enrichment ratios for leucine (0.76 +/- 0.06) and phenylalanine (0.77 +/- 0.06) were higher (P < 0.01) than the F/M ratios for glycine (0.18 +/- 0.04) and proline (0.22 +/- 0.02). This suggests that these two essential amino acids rapidly cross the placenta in vivo. Compared with the essentials, both glycine and proline had significantly lower F/M enrichment ratios, which were not different from each other. The results support the hypothesis that amino acids with high affinity for exchange transporters cross the placenta most rapidly. In intrauterine growth-restricted pregnancies, the F/M enrichment ratio was significantly lower (P < 0.01) for L-[1-13C]leucine (0.76 +/- 0.06 vs. 0.48 +/- 0.07) and for L-[1-13C]phenylalanine (0.77 +/- 0.06 vs. 0.46 +/- 0.07) compared with appropriate for gestational age pregnancies reflecting impaired transplacental flux. The F/M enrichment ratio did not differ for [1-13C]glycine (0.18 +/- 0.04 vs. 0.17 +/- 0.03), and L-[1-13C]proline (0.22 +/- 0.02 vs. 0.18 +/- 0.04).

Placental mTOR links maternal nutrient availability to fetal growth

“…This transporter has been reported to have reduced activity in both MVM and BM in association with IUGR [21], and to have increased activity in MVM from diabetic pregnancies giving rise to LGA babies [19]. These in vitro data are compatible with in vivo data showing a reduction of the transfer of the essential amino acids leucine and phenylalanine in IUGR [22]. The downregulation of amino acid transporters in IUGR could be the cause of the reduced fetal plasma amino acid concentrations seen in this pregnancy complication [23].…”

Maternal and fetal tryptophan metabolism in gestating rats: effects of intrauterine growth restriction

“…Further, both system A and system L activities are lower in isolated placental membranes from human pregnancies with IUGR, affecting amino acid levels in the fetus Lin et al 2012). When labelled phenylalanine and leucine boluses are injected intravenously in mothers undergoing C-section, the fetal/maternal (F/M) ratio of tracer enrichment is lower in IUGR than in control pregnancies (Paolini et al 2001). Little is known about the maternal-fetal transfer of l-tryptophan (l-Trp); although l-Trp transport in placental plasma membrane by system L transporters is lower with IUGR (Lager and Powell 2012) and IUGR fetuses have lower Trp concentrations (−24 %) (Lin et al 2012), the maternal and fetal metabolism of tryptophan has not, to our knowledge, been assessed using in vivo tracer kinetics.…”

Essential Roles of L-Type Amino Acid Transporter 1 in Syncytiotrophoblast Development by Presenting Fusogenic 4F2hc

“…In the human term placenta, LAT1 has been colocalized with 4F2hc at two polarized plasma membrane domains of the syncytiotrophoblast, i.e., the maternally facing apical membrane and the fetally facing basal membrane (22,25,26), implying the importance of LAT1-4F2hc heterodimer in the maternofetal transfer of amino acids. Based on studies using primary human trophoblasts, it has been proposed that abrogated cell surface localization of LAT1 may be implicated in intrauterine growth restriction (IUGR) (27,28), in which placental amino acid transport is impaired (29,30). To further understand the physiological relevance of LAT1 in vivo, we constructed a LAT1 knockout mouse strain.…”