Amniotic fluid (AF) is a complex substance essential to fetal well-being. This article reviews recent discoveries and the current understanding of the origin and circulation of AF and its nutritive, protective, and diagnostic functions. Future directions for AF research are also discussed.

Amniotic fluid: not just fetal urine anymore.

Tryptophan (Trp) requirements in pregnancy are several-fold: (1) the need for increased protein synthesis by mother and for fetal growth and development; (2) serotonin (5-HT) for signalling pathways; (3) kynurenic acid (KA) for neuronal protection; (4) quinolinic acid (QA) for NAD+ synthesis (5) other kynurenines (Ks) for suppressing fetal rejection. These goals could not be achieved if maternal plasma [Trp] is depleted. Although plasma total (free + albumin-bound) Trp is decreased in pregnancy, free Trp is elevated. The above requirements are best expressed in terms of a Trp utilization concept. Briefly, Trp is utilized as follows: (1) In early and mid-pregnancy, emphasis is on increased maternal Trp availability to meet the demand for protein synthesis and fetal development, most probably mediated by maternal liver Trp 2,3-dioxygenase (TDO) inhibition by progesterone and oestrogens. (2) In mid- and late pregnancy, Trp availability is maintained and enhanced by the release of albumin-bound Trp by albumin depletion and non-esterified fatty acid (NEFA) elevation, leading to increased flux of Trp down the K pathway to elevate immunosuppressive Ks. An excessive release of free Trp could undermine pregnancy by abolishing T-cell suppression by Ks. Detailed assessment of parameters of Trp metabolism and disposition and related measures (free and total Trp, albumin, NEFA, K and its metabolites and pro- and anti-inflammatory cytokines in maternal blood and, where appropriate, placental and fetal material) in normal and abnormal pregnancies may establish missing gaps in our knowledge of the Trp status in pregnancy and help identify appropriate intervention strategies.

Tryptophan metabolism, disposition and utilization in pregnancy.

Both animal and human studies have shown that maternal stress or anxiety during pregnancy is associated with increased risk of disturbance in offspring neurodevelopment and behaviour. In animal models, increased foetal exposure to glucocorticoids has been found to be one mechanism for such foetal programming. Little is understood of the mediating mechanisms in humans, and one aim of our research programme is to investigate this further. This review presents a synopsis of some of our recent results. We aimed to test the hypothesis that maternal anxiety was associated with raised maternal cortisol, and that this in turn was related to increased foetal exposure to cortisol. We studied this by recruiting women at amniocentesis, obtained their Spielberger State Anxiety scores, and assessed maternal plasma cortisol and amniotic fluid cortisol. We also examined maternal plasma and amniotic fluid testosterone levels. Awaiting amniocentesis was in general anxiogenic, but with a wide range of anxiety scores. Maternal anxiety was significantly associated with plasma cortisol before 17 weeks, albeit of modest magnitude (r = 0.0.23), and not after 17 weeks of gestation. This is probably due to the known attenuation of the maternal hypothalamic-pituitary-adrenal axis with increasing gestation. We found a strong correlation between maternal plasma and amniotic fluid cortisol levels, which increased with gestation and became robust after 18 weeks. This correlation increased with maternal anxiety, suggesting a possible effect of maternal mood on placental function. There was a positive correlation between cortisol and testosterone in amniotic fluid, in both male and female foetuses independent of maternal anxiety, plasma testosterone, gestational age, and time of collection. Foetal stress may be associated with increased foetal exposure to testosterone. However, maternal anxiety did not predict amniotic fluid cortisol or testosterone level. Thus, the role of these hormones in mediating the effect of maternal mood on foetal development in humans remains to be demonstrated.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2826.2008.01659.x

Maternal antenatal anxiety and amniotic fluid cortisol and testosterone: possible implications for foetal programming.

Fetal growth depends on placental transfer of amino acids from maternal to fetal blood. The mechanisms of net amino acid efflux across the basal membrane (BM) of the placental syncytiotrophoblast to the fetus, although vital for amino acid transport, are poorly understood. We examined the hypothesis that facilitated diffusion by the amino acid transporters TAT1, LAT3 and LAT4 plays an important role in this process, with possible effects on fetal growth. Amino acid transfer was measured in isolated perfused human placental cotyledons (n = 5 per experiment) using techniques which distinguish between different transport processes. Placental TAT1, LAT3 and LAT4 proteins were measured, and mRNA expression levels (measured using real-time quantitative-PCR) were related to fetal and neonatal anthropometry and dual-energy X-ray absorptiometry measurements of neonatal lean mass in 102 Southampton Women's Survey (SWS) infants. Under conditions preventing transport by amino acid exchangers, all amino acids appearing in the fetal circulation were substrates of TAT1, LAT3 or LAT4. Western blots demonstrated the presence of TAT1, LAT3 and LAT4 in placental BM preparations. Placental TAT1 and LAT3 mRNA expression were positively associated with measures of fetal growth in SWS infants (P < 0.05). We provide evidence that the efflux transporters TAT1, LAT3 and LAT4 are present in the human placental BM, and may play an important role in the net efflux of amino acids to the fetus. Unlike other transporters they can increase fetal amino acid concentrations. Consistent with a role in placental amino acid transfer capacity and fetal growth TAT1 and LAT3 mRNA expression showed positive associations with infant size at birth.

Facilitated transporters mediate net efflux of amino acids to the fetus across the basal membrane of the placental syncytiotrophoblast.

Human Nutrition and Dietetics. By SIR STANLEY DAVIDSON, R. PASSMORE and J. F. BROCK. Fifth edition. Pp. 597, illustrated. Edinburgh and London: Churchill Livingstone, 1972. £6.00. The Acute Abdomen in Rhyme. By SIR ZACHARY COPE. Fifth edition. Pp. 108, illustrated. London: H. K. Lewis, 1972. £0.50. Multiple Sclerosis. A reappraisal. By D. McALPINE, C. E. LUMSDEN and E. D. ACHESON. Second edition. Pp. 653, illustrated. Edinburgh and London: Churchill Livingstone, 1972. £6.00. The UFA W Handbook on the Care and Management of Laboratory Animals. Edited by UFAW. Foreword by C. W. HuME. Fourth edition. Pp. 624, illustrated. London: Churchill Livingstone, 1972. £7.00. Clinical Electroencephalography. By L. G. KILOH, A. J. MCCOMAS and J. W. OSSELTON. Third Edition. Pp. 239, illustrated. London: Butterworths, 1972. £6.50.

The Upper Cervical Spine. Regional Anatomy, Pathology and Traumatology. A Systematic Radiological Atlas and Textbook.

The concentration of 23 free amino acids was measured in homogenates of fetal liver and samples of fetal plasma from 20 pregnancies between 12 and 17 weeks gestation and compared with those found in matched samples of maternal plasma and amniotic fluid. A feto-maternal plasma concentration gradient was observed for 21 amino acids indicating that the feto-maternal amino acid gradient across the placenta is established from very early in pregnancy. The amino acid concentration pattern was similar in fetal plasma and amniotic fluid but different in fetal liver, supporting the concept that it is essentially placental transport and metabolism that provides the fetus with these molecules. The highest amino acid concentration was found for glutamine in fetal plasma and glutamic acid in fetal liver. Very low concentrations of glutamic acid in fetal plasma suggest that this amino acid is actively taken up by the fetal liver. Citrulline, alpha-aminobutyric acid, methionine, arginine and tryptophan were not measurable in fetal liver tissue, indicating that this organ has a limited role in utero in the metabolism of these amino acids. Significant positive correlations were found between fetal plasma and amniotic fluid for the concentration of most amino acids whereas only the concentration of threonine was found to be positively correlated between fetal liver and plasma. These results suggest that during the second trimester passive diffusion through the unkeratinized fetal skin is the main pathway for amino acids between the fetal circulation and the amniotic cavity.

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Erik Gerloo

Papers

Free amino acids in human fetal liver and fluids at 12–17 weeks of gestation