Placental amino acid transport systems and fetal growth restriction--a workshop report.
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Amino Acid Transport System A↗
Biomedical subjects
A M Marconi
Publications and source records attributed to A M Marconi.
Undesired effects of steroids during pregnancy.
Antenatal corticosteroid administration for enhancing fetal lung maturity can be expected to induce negative maternal and fetal side-effects. Maternal short-term effects after multiple courses of corticosteroids are an increase of infections and a higher incidence of endometritis and chorionamnionitis in patients with premature rupture of membranes. A single dose of corticosteroid induces an increase in the count of maternal white blood cells and metabolic effects such as the augmentation of amino acid concentration and of fasting glucose levels in maternal plasma. Negative fetal effects of antenatal corticosteroids are a reduction of fetal body and breathing movements and a reduction of fetal heart rate variation, without any changes in Doppler waveform patterns of fetoplacental vessels. It has been suggested that a multiple course of corticosteroids antenatally might induce negative effects on fetal intrauterine growth and on neonatal birth weight. In addition, multiple courses are associated with an increased risk of early-onset neonatal sepsis.
Betamethasone↗
Advanced tubal pregnancy associated with severe fetal growth restriction: a case report.
A case is described of advanced tubal pregnancy associated with severe fetal growth restriction delivered at 27 weeks. The placenta was implanted on the salpinx and on the uterotubal angle. Progressing tubal pregnancy and its placental histological characteristics could be a model of placental dysfunction typically associated with intrauterine growth restriction.
Adult↗
Placental transport of leucine, phenylalanine, glycine, and proline in intrauterine growth-restricted pregnancies.
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).
Adult↗
Umbilical amino acid uptake at increasing maternal amino acid concentrations: effect of a maternal amino acid infusate.
OBJECTIVE: Our purpose was to establish whether, in normal human pregnancies, the maternal intravenous infusion of amino acids can increase fetal amino acid uptake and amino acid concentrations. STUDY DESIGN: Twenty-six normal pregnancies were studied at the time of cesarean delivery (38-40 weeks' gestation). In 10 cases an amino acid formulation (Freamine 8.5% III, Baxter) was infused into a maternal vein before cesarean delivery. Maternal blood samples were obtained during the course of the study. Umbilical venous and arterial samples were obtained from the clamped segment of the cord. There were no differences between the 2 groups for fetal and placental weights and for fetal oxygenation and acid-base balance. RESULTS: Maternal amino acid concentrations increased significantly in the group receiving infusions. Significant increases in umbilical venous concentrations were observed for most amino acids, except for histidine and threonine. The amino acid umbilical arteriovenous differences per mole of oxygen (AA/O(2) ratio) increased significantly for leucine, isoleucine, valine, methionine, phenylalanine, arginine, glycine, serine, alanine, and proline. There were no significant increases for lysine, histidine, and threonine. CONCLUSION: An increase in maternal concentrations leads to an increase in the delivery of most amino acids to the fetus.
Adult↗
Identification and sequencing of beta-myrcene catabolism genes from Pseudomonas sp. strain M1.
The M1 strain, able to grow on beta-myrcene as the sole carbon and energy source, was isolated by an enrichment culture and identified as a Pseudomonas sp. One beta-myrcene-negative mutant, called N22, obtained by transposon mutagenesis, accumulated (E)-2-methyl-6-methylen-2,7-octadien-1-ol (or myrcen-8-ol) as a unique beta-myrcene biotransformation product. This compound was identified by gas chromatography-mass spectrometry. We cloned and sequenced the DNA regions flanking the transposon and used these fragments to identify the M1 genomic library clones containing the wild-type copy of the interrupted gene. One of the selected cosmids, containing a 22-kb genomic insert, was able to complement the N22 mutant for growth on beta-myrcene. A 5,370-bp-long sequence spanning the region interrupted by the transposon in the mutant was determined. We identified four open reading frames, named myrA, myrB, myrC, and myrD, which can potentially code for an aldehyde dehydrogenase, an alcohol dehydrogenase, an acyl-coenzyme A (CoA) synthetase, and an enoyl-CoA hydratase, respectively. myrA, myrB, and myrC are likely organized in an operon, since they are separated by only 19 and 36 nucleotides (nt), respectively, and no promoter-like sequences have been found in these regions. The myrD gene starts 224 nt upstream of myrA and is divergently transcribed. The myrB sequence was found to be completely identical to the one flanking the transposon in the mutant. Therefore, we could ascertain that the transposon had been inserted inside the myrB gene, in complete agreement with the accumulation of (E)-2-methyl-6-methylen-2,7-octadien-1-ol by the mutant. Based on sequence and biotransformation data, we propose a pathway for beta-myrcene catabolism in Pseudomonas sp. strain M1.
Acyclic Monoterpenes↗
Steady state maternal-fetal leucine enrichments in normal and intrauterine growth-restricted pregnancies.
The aim of this study was to compare the fetal/maternal (F/M) leucine-enrichment ratio in normal (AGA) and intrauterine growth-restricted (IUGR) pregnancies at the time of fetal blood sampling (FBS). A maternal primed-constant infusion of L-[1-13C]-leucine was given in six AGA and 14 IUGR pregnancies, divided into three groups according to the pulsatility index (PI) of the umbilical artery and to fetal heart rate (FHR): group 1 (normal FHR and PI, four cases); group 2 (normal FHR and abnormal PI, five cases); and group 3 (abnormal FHR and PI, five cases). Maternal arterialized samples were taken at time zero and every 20 min for 125+/-7 min. Umbilical venous samples were obtained after 114+/-42 min of infusion. Under steady state conditions, there was a significant linear relationship between maternal leucine disposal rate and maternal leucine concentration. The comparison of fetal to maternal leucine enrichment showed a progressive dilution of the fetal enrichment relative to the mother between AGA and IUGR of group 1 (0.89 versus 0.78, p < 0.02), group 2 (0.71, p < 0.001), and group 3 (0.62, p < 0.001), and also among the three IUGR groups. The F/M leucine molar percent enrichment (MPE) ratio showed a positive correlation with the umbilical venous oxygen content and an inverse correlation with fetal lactate concentration. We conclude that the dilution in the fetal/maternal leucine-enrichment ratio correlates with the severity of growth restriction and reflects decreased transplacental leucine flux and/or increased protein breakdown within the fetoplacental compartments.
Adult↗
Pathophysiology of intrauterine growth retardation: role of the placenta.
The placenta is essential for normal fetal development. Failure of the placenta can result in many fetal conditions, for example, intrauterine growth retardation (IUGR). Placentas from pregnancies complicated by IUGR show vascular damage, which may lead to the onset of pregnancy-induced maternal hypertension. Accurate placental assessment may, therefore, indicate which fetuses are at risk of IUGR and so improve clinical evaluation and management of both the fetus and the mother. Placental development and function can be assessed by a number of methods, including measurement of placental weight at mid-gestation (placental growth in the second trimester correlates strongly with placental weight at birth), assessment of fetal and placental circulation (an association between perinatal morbidity and abnormal blood velocity profiles has been established) and assessment of placental metabolism and nutritional transfer (a reduction in transfer of nutrients may be an early indicator of IUGR.
Female↗
Sequencing and functional analysis of styrene catabolism genes from Pseudomonas fluorescens ST.
The nucleotide sequence of the 4,377-bp chromosomal region of Pseudomonas fluorescens ST that codes for the oxidation of styrene to phenylacetic acid was determined. Four open reading frames, named styA, styB, styC, and styD, were identified in this region. Sequence analysis and biotransformation assays, performed with batch and continuous cultures, allowed us to identify the functions of the sequenced genes. styA and styB encode a styrene monooxygenase responsible for the transformation of styrene to epoxystyrene; styC codes for the second enzyme of the pathway, an epoxystyrene isomerase that converts epoxystyrene to phenylacetaldehyde; and the styD gene produces a phenylacetaldehyde dehydrogenase that oxidizes phenylacetaldehyde to phenylacetic acid. StyA, 415-amino-acids long, was found to be weakly homologous to p-hydroxybenzoate hydroxylase from both P. fluorescens and P. aeruginosa and to salicylate hydroxylase from P. putida, suggesting that it might be a flavin adenine dinucleotide-binding monooxygenase. StyB was found to be partially homologous to the carboxyterminal part of the 2,4-dichlorophenol-6-monooxygenase encoded by plasmid pJP4, while the styC product did not share significant homology with any known proteins. The fourth open reading frame, styD, could encode a protein of 502 amino acids and was strongly homologous to several eukaryotic and prokaryotic aldehyde dehydrogenases. The order of the genes corresponds to that of the catabolic steps. The previously suggested presence of the gene for epoxystyrene reductase, which directly converts epoxystyrene to 2-phenylethanol (A.M. Marconi, F. Beltrametti, G. Bestetti, F. Solinas, M. Ruzzi, E. Galli, and E. Zennaro, Appl. Environ. Microbiol. 61:121-127, 1996), has not been confirmed by sequencing and by biotransformation assays performed in continuous cultures. A copy of the insertion sequence ISI162, belonging to the IS21-like family of elements, was identified immediately downstream of the styrene catabolic genes.
Base Sequence↗
Association between the activity of the system A amino acid transporter in the microvillous plasma membrane of the human placenta and severity of fetal compromise in intrauterine growth restriction.
Primarily, our objectives were to compare system A amino acid transporter activity in the microvillous plasma membrane (MVM) of placentas from normally grown (appropriate for gestational age, AGA) and intrauterine growth-restricted (IUGR) fetuses delivered during the third trimester, as a whole and in relation to the severity of IUGR. Ten AGA and 16 IUGR pregnancies were studied at the time of elective cesarean section performed between 28 and 40 wk of gestation. Severity of IUGR pregnancies was assessed primarily by Doppler velocimetry and fetal heart rate monitoring. Placental MVM vesicles were prepared, and system A activity in these was measured. The transporter activity was significantly lower in IUGR compared with AGA pregnancies. Within the IUGR group system A activity was only significantly lower, compared with AGA, in cases that presented with a reduction in umbilical blood flow. We conclude that placental MVM system A activity is lower in IUGR compared with AGA pregnancies delivered during the third trimester. System A activity is related to the severity of IUGR.
Alkaline Phosphatase↗
The new obstetrics: its integration into neonatal clinical practise, teaching and research.
Most neonatologists have not yet incorporated into their teaching, clinical service and research the advances in high risk obstetrics particularly as it relates to fetal surveillance. This brief review emphasizes some of the "new obstetrics" from the viewpoint of perinatal medicine, particularly in terms of neonatal teaching and the design of future neonatal research. The information that can be obtained about an infant prenatally by the use of ultrasound. power doppler, computerized fetal heart rate monitoring, cordocentesis, etc is extensive and yet, has rarely been utilized in the design of neonatal research protocols. It is becoming imperative that the "new obstetrics" be recognized and utilized in modern neonatal thinking if a truly "perinatal medicine" is to be practised.
Cordocentesis↗
The impact of gestational age and fetal growth on the maternal-fetal glucose concentration difference.
OBJECTIVE: To test whether the human fetus accommodates to the increasing glucose requirements of late pregnancy with an increased maternal-fetal glucose concentration gradient and whether there are differences in pregnancies with fetal growth restriction (FGR) according to clinical severity. METHODS: Umbilical venous glucose concentration was measured in 77 normal pregnancies (appropriate for gestational age [AGA]) and 42 pregnancies complicated by FGR at the time of fetal blood sampling. In 40 AGA and in all FGR cases, a maternal "arterialized" blood sample was collected simultaneously. Growth-restricted fetuses were subdivided into three groups according to fetal heart rate (FHR) recordings and Doppler measurements of the umbilical artery pulsatility index (PI): group 1 (normal FHR and PI; 12 cases), group 2 (normal FHR, abnormal PI; 17 cases) and group 3 (abnormal FHR and PI; 13 cases). RESULTS: In normal pregnancies with increasing gestational age, there was a significant decrease (P < .001) of umbilical venous glucose concentration and a significant increase of the maternal-fetal glucose concentration difference (P < .001). In addition, there was a significant relation between fetal and maternal glucose concentrations (P < .001). In FGR pregnancies, the maternal-fetal glucose concentration difference was significantly higher in fetuses of groups 2 and 3 compared with normal pregnancies and FGR pregnancies of group 1. CONCLUSION: In human pregnancy, the fetal glucose concentration is a function of both gestational age and the maternal glucose concentration. In FGR pregnancies, as an accommodation of the fetus to a restricted placental size and placental glucose transport capacity, the maternal-fetal glucose concentration difference is increased, and this increase is a function of the clinical severity.
Adult↗
Maternal concentrations and fetal-maternal concentration differences of plasma amino acids in normal and intrauterine growth-restricted pregnancies.
OBJECTIVES: Our purpose was to determine whether maternal amino acid concentration changes during gestation in pregnancies with intrauterine growth restriction as in normal pregnancies and to verify whether these changes are related to changes in fetal-maternal differences. STUDY DESIGN: Amino acid concentrations were measured in 5 nonpregnant women, in 11 second-trimester and 10 third-trimester pregnant women with appropriate-for-gestational-age fetuses, and in 23 pregnant women with intrauterine growth restriction. Umbilical venous amino acids were measured at the time of fetal blood sampling. The severity of intrauterine growth restriction was assessed by Doppler velocimetry and fetal heart rate and by evaluation of oxygenation and acid-base balance. RESULTS: In normal pregnant women the maternal concentration of most amino acids was significantly lower in both the second and third trimesters compared with nonpregnant women. In intrauterine growth restriction the maternal concentrations of most essential amino acids were significantly higher than in appropriate-for-gestational-age pregnancies. This observation, coupled with lower fetal amino acid concentrations in intrauterine growth restriction, leads to significantly lower fetal-maternal differences. CONCLUSIONS: Normal pregnant women have a significant decrease in amino acid concentrations compared with nonpregnant women, whereas in intrauterine growth restriction maternal amino acids are reduced less, Significantly lower fetal-maternal concentration differences are present in intrauterine growth restriction, independent of the degree of severity.
Adult↗
Cloning and characterization of styrene catabolism genes from Pseudomonas fluorescens ST.
A gene bank from Pseudomonas fluorescens ST was constructed in the broad-host-range cosmid pLAFR3 and mobilized into Pseudomonas putida PaW340. Identification of recombinant cosmids containing the styrene catabolism genes was performed by screening transconjugants for growth on styrene and epoxystyrene. Transposon mutagenesis and subcloning of one of the selected genome fragments have led to the identification of three enzymatic activities: a monooxygenase activity encoded by a 3-kb PstI-EcoRI fragment and an epoxystyrene isomerase activity and an epoxystyrene reductase activity encoded by a 2.3-kb BamHI fragment. Escherichia coli clones containing the 3-kb PstI-EcoRI fragment were able to transform styrene into epoxystyrene, and those containing the 2.3-kb BamHI fragment converted epoxystyrene into phenylacetaldehyde or, only in the presence of glucose, into 2-phenylethanol. The three genes appear to be clustered and are probably encoded by the same DNA strand. In E. coli, expression of the epoxystyrene reductase gene was under the control of its own promoter, whereas the expression of the other two genes was dependent on the presence of an external vector promoter.
Acetaldehyde↗
Characterization and sequence of a novel insertion sequence, IS1162, from Pseudomonas fluorescens.
We have determined the nucleotide sequence of IS1162, a new insertion sequence (IS) isolated from Pseudomonas fluorescens (Pf) strain ST. This IS element is present in two copies on the pEG plasmid harboured by Pf ST and in a single copy on the chromosome, adjacent to the styrene catabolic genes. IS1162 is 2634 bp in length with 12-bp terminal inverted repeats (IR), and could encode four proteins (ORFs), two for each strand. One strand, Pro1 (62,990 Da), showed a helix-turn-helix motif at the N-terminal region, and Pro2 (25,997 Da) was characterized by the presence of the A and B motives of the NTP (ATP/GTP)-binding site. Comparison of IS1162 of Pf with known IS showed a high homology with IS408 of Burkholderia cepacia [Byrne and Lessie, Plasmid 31 (1994) 138-147]. Pro1 and Pro2 were found to be homologous to the corresponding ORFs of IS408, IS21 [Reimmann et al., Mol. Gen. Genet. 215 (1989) 416-424], IS232 [Menou et al., J. Bacteriol. 172 (1990) 6689-6696] and IS5376 [Xu et al., Plasmid 29 (1993) 1-9]. IS1162 transposed at low frequency and no cointegrates were found among the transposition products. The target duplication sites, variable in length, showed the presence of homologous motives, suggesting a certain degree of specificity of the IS1162 insertion site.
Amino Acid Sequence↗
Genetic amniocentesis in biamniotic twin pregnancies by a single transabdominal insertion of the needle.
We present a technique to aspirate amniotic fluid from both sacs in biamniotic twin pregnancies using a single abdominal insertion with a spinal needle. It was successful in 48 out of 55 cases of biamniotic twin pregnancies referred to our perinatal unit between 1985 and 1994. The single insertion technique was used when the inter-amniotic membrane was clearly evident and two separate free amniotic fluid pools could be reached by the operator with a single puncture. An adequate amount of amniotic fluid was sampled from both sacs to make a cytogenetic diagnosis in all cases. There were four fetuses with trisomy 21 in three twin pregnancies. In two cases, only one twin was affected whilst the co-twin was normal, so that a selective feticide was performed. No miscarriages due to genetic amniocentesis were reported. After 1990, all genetic amniocenteses in biamniotic twin pregnancies (except for one case due to late booking) were performed between 14 and 15 weeks of gestation and with all cases except one, it was possible to sample both twins by a single puncture. We suggest that early amniocentesis (14-15 weeks) by a single abdominal puncture could be a reliable and safe alternative to first-trimester chorionic villus sampling in twin pregnancies.
Amniocentesis↗
In vivo placental transport of glycine and leucine in human pregnancies.
L-[1-13C]Glycine and L-[1-13C]leucine were infused as a bolus into 12 pregnant patients carrying normal fetuses before fetal blood sampling at gestational ages ranging from 20 to 37 wk. Maternal venous samples were obtained every 2-3 min for 15 min after the bolus infusion. Fetal samples were obtained from the umbilical vein within 15 min of the bolus. Amino acid plasma enrichments (molar percent enrichment) were determined by gas chromatography-mass spectroscopy and their concentrations by ion exchange chromatography. The ratios of glycine and leucine transfer were assessed from fetal/maternal enrichment ratios for each amino acid. We now report that over the gestational age range of 20-37 wk, under relatively undisturbed fetomaternal conditions (fetal blood sampling), human placental glycine transfer is limited, with a glycine/leucine ratio = 0.16 +/- 0.02. We hypothesize that, in human pregnancies, the relative rates of in vivo transplancental transport of amino acids can be assessed indirectly utilizing fetal blood sampling and stable isotope methodology. The application of this approach to leucine and glycine demonstrates that the transfer of leucine is rapid (demonstrable in seconds), whereas that of glycine is more limited.
Adult↗
Fetal blood sampling during pregnancy: risks and diagnostic advantages.
A review is provided on the use of fetal blood sampling during pregnancy. Informations on the technique, its indications, risks and benefits are provided. In addition, the application of fetal blood sampling in cases of intrauterine growth retardation as well as some metabolic features of intrauterine life are discussed.
Blood Specimen Collection↗