Abstract
Taurine is regarded as an essential amino acid in utero, and fetal taurine supply is believed to rely solely on placental transfer from maternal plasma. Despite its potential role in intrauterine growth restriction and other developmental disturbances, human in vivo studies of taurine transfer between the maternal, placental, and fetal compartments are scarce. We studied placental transfer of taurine in uncomplicated human term pregnancies in vivo in a cross-sectional study of 179 mother-fetus pairs. During cesarean section, we obtained placental tissue and plasma from incoming and outgoing vessels on the maternal and fetal sides of the placenta. Taurine was measured by liquid chromatography–tandem mass spectrometry. We calculated paired arteriovenous differences, and measured placental expression of the taurine biosynthetic enzyme cysteine sulfinic acid decarboxylase (CSAD) with quantitative real-time polymerase chain reaction and western blot. We observed a fetal uptake (p < 0.001), an uteroplacental release (p < 0.001), and a negative placental consumption of taurine (p = 0.001), demonstrating a bilateral placental release to the maternal and fetal compartments. Increasing umbilical vein concentrations and fetal uptake was associated with the uteroplacental release to the maternal circulation (rs = − 0.19, p = 0.01/rs = − 0.24, p = 0.003), but not with taurine concentrations in placental tissue. CSAD-mRNA was expressed in placental tissue, suggesting a potential for placental taurine synthesis. Our observations show that the placenta has the capacity to a bilateral taurine release, indicating a fundamental role of taurine in the human placental homeostasis beyond the supply to the fetus.
Similar content being viewed by others
References
Alterman MA, Hunziker P (2011) Amino acid analysis: methods and protocols. Humana Press, USA
Boujendar S, Reusens B, Merezak S, Ahn MT, Arany E, Hill D, Remacle C (2002) Taurine supplementation to a low protein diet during foetal and early postnatal life restores a normal proliferation and apoptosis of rat pancreatic islets. Diabetologia 45(6):856–866. https://doi.org/10.1007/s00125-002-0833-6
Cetin I, Marconi AM, Bozzetti P, Sereni LP, Corbetta C, Pardi G, Battaglia FC (1988) Umbilical amino acid concentrations in appropriate and small for gestational age infants: a biochemical difference present in utero. Am J Obstet Gynecol 158(1):120–126
Cetin I, Corbetta C, Sereni LP, Marconi AM, Bozzetti P, Pardi G, Battaglia FC (1990) Umbilical amino acid concentrations in normal and growth-retarded fetuses sampled in utero by cordocentesis. Am J Obstet Gynecol 162(1):253–261
Cetin I, Ronzoni S, Marconi AM, Perugino G, Corbetta C, Battaglia FC, Pardi G (1996) Maternal concentrations and fetal-maternal concentration differences of plasma amino acids in normal and intrauterine growth-restricted pregnancies. Am J Obstet Gynecol 174(5):1575–1583
Cetin I, de Santis MS, Taricco E, Radaelli T, Teng C, Ronzoni S, Spada E, Milani S, Pardi G (2005) Maternal and fetal amino acid concentrations in normal pregnancies and in pregnancies with gestational diabetes mellitus. Am J Obstet Gynecol 192(2):610–617. https://doi.org/10.1016/j.ajog.2004.08.011
Desforges M, Parsons L, Westwood M, Sibley CP, Greenwood SL (2013) Taurine transport in human placental trophoblast is important for regulation of cell differentiation and survival. Cell Death Dis 4:e559. https://doi.org/10.1038/cddis.2013.81
Desforges M, Whittaker H, Farmer E, Sibley CP, Greenwood SL (2015) Effects of taurine depletion on human placental syncytiotrophoblast renewal and susceptibility to oxidative stress. Adv Exp Med Biol 803:63–73. https://doi.org/10.1007/978-3-319-15126-7_6
Ditchfield AM, Desforges M, Mills TA, Glazier JD, Wareing M, Mynett K, Sibley CP, Greenwood SL (2015) Maternal obesity is associated with a reduction in placental taurine transporter activity. Int J Obes (Lond) 39(4):557–564. https://doi.org/10.1038/ijo.2014.212
Gaull G, Sturman JA, Raiha NC (1972) Development of mammalian sulfur metabolism: absence of cystathionase in human fetal tissues. Pediatr Res 6(6):538–547. https://doi.org/10.1203/00006450-197206000-00002
Haugen G, Kiserud T, Godfrey K, Crozier S, Hanson M (2004) Portal and umbilical venous blood supply to the liver in the human fetus near term. Ultrasound Obstet Gynecol 24(6):599–605. https://doi.org/10.1002/uog.1744
Hayashi S, Sanada K, Sagawa N, Yamada N, Kido K (1978) Umbilical vein-artery differences of plasma amino acids in the last trimester of human pregnancy. Biol Neonate 34(1–2):11–18
Hayes KC, Sturman JA (1981) Taurine in metabolism. Annu Rev Nutr 1:401–425. https://doi.org/10.1146/annurev.nu.01.070181.002153
Hibbard JU, Pridjian G, Whitington PF, Moawad AH (1990) Taurine transport in the in vitro perfused human placenta. Pediatr Res 27(1):80–84. https://doi.org/10.1203/00006450-199001000-00021
Holm MB, Bastani NE, Holme AM, Zucknick M, Jansson T, Refsum H, Morkrid L, Blomhoff R, Henriksen T, Michelsen TM (2017) Uptake and release of amino acids in the fetal-placental unit in human pregnancies. PLoS One 12(10):e0185760. https://doi.org/10.1371/journal.pone.0185760
Holme AM, Holm M, Roland MC, Horne H, Michelsen TM, Haugen G, Henriksen T (2017) The 4-vessel sampling approach to integrative studies of human placental physiology in vivo. J Vis Exp (126). https://doi.org/10.3791/55847
Hultman K, Alexanderson C, Manneras L, Sandberg M, Holmang A, Jansson T (2007) Maternal taurine supplementation in the late pregnant rat stimulates postnatal growth and induces obesity and insulin resistance in adult offspring. J Physiol 579(Pt 3):823–833. https://doi.org/10.1113/jphysiol.2006.124610
Jozwik M, Teng C, Battaglia FC, Meschia G (1999) Fetal supply of amino acids and amino nitrogen after maternal infusion of amino acids in pregnant sheep. Am J Obstet Gynecol 180(2 Pt 1):447–453
Karl PI, Fisher SE (1990) Taurine transport by microvillous membrane vesicles and the perfused cotyledon of the human placenta. Am J Physiol 258(3 Pt 1):C443–C451
Korneeva KL, Rodriguez RR, Ralchenko SV, Martunovska OV, Frolova AO, Martsenyuk OP, Manzhula LV, Melnyk VT, Shkoropad OY, Obolenska MY (2016) Expression of genes, encoding the enzymes of cysteine metabolism in human placenta in the first and third trimesters of uncomplicated pregnancy. Ukrain Biochem J 88(1):88–98. https://doi.org/10.15407/ubj88.01.088
Liu J, Liu L, Chen H (2011) Antenatal taurine supplementation for improving brain ultrastructure in fetal rats with intrauterine growth restriction. Neuroscience 181:265–270. https://doi.org/10.1016/j.neuroscience.2011.02.056
Miyamoto Y, Balkovetz DF, Leibach FH, Mahesh VB, Ganapathy V (1988) Na+ + Cl−-gradient-driven, high-affinity, uphill transport of taurine in human placental brush-border membrane vesicles. FEBS Lett 231(1):263–267
Norberg S, Powell TL, Jansson T (1998) Intrauterine growth restriction is associated with a reduced activity of placental taurine transporters. Pediatr Res. https://doi.org/10.1203/00006450-199808000-00016
Park E, Park SY, Cho IS, Kim BS, Schuller-Levis G (2017) A novel cysteine sulfinic acid decarboxylase knock-out mouse: taurine distribution in various tissues with and without taurine supplementation. Adv Exp Med Biol 975:461–474. https://doi.org/10.1007/978-94-024-1079-2_37
Philipps AF, Holzman IR, Teng C, Battaglia FC (1978) Tissue concentrations of free amino acids in term human placentas. Am J Obstet Gynecol 131(8):881–887
Prenton MA, Young M (1969) Umbilical vein-artery and uterine arterio-venous plasma amino acid differences (in the human subject). J Obstet Gynaecol Br Commonw 76(5):404–411
Rigano S, Ferrazzi E, Boito S, Pennati G, Padoan A, Galan H (2010) Blood flow volume of uterine arteries in human pregnancies determined using 3D and bi-dimensional imaging, angio-Doppler, and fluid-dynamic modeling. Placenta 31(1):37–43. https://doi.org/10.1016/j.placenta.2009.10.010
Ripps H, Shen W (2012) Review: taurine: a “very essential” amino acid. Mol Vis 18:2673–2686
Roos S, Powell TL, Jansson T (2004) Human placental taurine transporter in uncomplicated and IUGR pregnancies: cellular localization, protein expression, and regulation. Am J Physiol Regul Integr Comp Physiol 287(4):R886–R893. https://doi.org/10.1152/ajpregu.00232.2004
Steingrimsdottir T, Ronquist G, Ulmsten U (1993) Balance of amino acids in the pregnant human uterus at term. Eur J Obstet Gynecol Reprod Biol 50(3):197–202
Stipanuk MH, Dominy JE Jr, Lee JI, Coloso RM (2006) Mammalian cysteine metabolism: new insights into regulation of cysteine metabolism. J Nutr 136(6 Suppl):1652s–1659s
Sturman JA, Rassin DK, Gaull GE (1970) Distribution of transsulphuration enzymes in various organs and species. Int J Biochem 1(2):251–253. https://doi.org/10.1016/0020-711X(70)90102-3
Tappaz ML (2004) Taurine biosynthetic enzymes and taurine transporter: molecular identification and regulations. Neurochem Res 29(1):83–96
Tsuchiya H, Matsui K, Muramatsu T, Ando T, Endo F (2009) Differences between the amino acid concentrations of umbilical venous and arterial blood. Arch Dis Child Fetal Neonatal Ed 94(2):F155–F156. https://doi.org/10.1136/adc.2008.147256
Vallejos C, Riquelme G (2007) The maxi-chloride channel in human syncytiotrophoblast: a pathway for taurine efflux in placental volume regulation? Placenta 28(11–12):1182–1191. https://doi.org/10.1016/j.placenta.2007.06.005
Velazquez A, Rosado A, Bernal A, Noriega L, Arevalo N (1976) Amino acid pools in the feto-maternal system. Biol Neonate 29(1–2):28–40
Winge I, Teigen K, Fossbakk A, Mahootchi E, Kleppe R, Sköldberg F, Kämpe O, Haavik J (2015) Mammalian CSAD and GADL1 have distinct biochemical properties and patterns of brain expression. Neurochem Int 90:173–184. https://doi.org/10.1016/j.neuint.2015.08.013
Acknowledgements
First, we would like to thank the participating women for contributing to our study. We would also like to acknowledge the anesthesiologists, specialist nurses, obstetricians, and midwives at Oslo University Hospital for offering their time and skills to help us with the sampling procedure. We further thank Trine M. Reine and Anne Randi Enget at the Department of Nutrition at the University of Oslo who performed the qRT-PCR analysis, and Jan Haavik at the Department of Biomedicine at the University of Bergen who generously provided the CSAD antibody for western blot analysis.
Funding
This study was funded by grants from the South-Eastern Norway Regional Health Authority, the Throne Holst foundation, the Norwegian National Advisory Unit on Women’s Health, Oslo University Hospital, and the Department of Obstetrics, Oslo University Hospital.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the data protection officials at Oslo University Hospital and the Regional Committee for Medical and Health Research Ethics, Southern Norway 2419/2011.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Conflict of interest
Rune Blomhoff is a chair holder in AS Vitas. Otherwise, the authors declare that they have no conflict of interest.
Additional information
Handling Editor: S. W. Schaffer.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Holm, M.B., Kristiansen, O., Holme, A.M. et al. Placental release of taurine to both the maternal and fetal circulations in human term pregnancies. Amino Acids 50, 1205–1214 (2018). https://doi.org/10.1007/s00726-018-2576-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00726-018-2576-9