Abstract
Taurine is an important nutrient in intrauterine life, being required for fetal organ development and cellular renewal of syncytiotrophoblast (STB), the nutrient transport epithelium of the placenta. As taurine is conditionally essential in human pregnancy, the fetal and placental demand for taurine is met by uptake from maternal blood into STB through the activity of TauT. Pre-eclampsia (PE) and maternal obesity are serious complications of pregnancy, associated with fetal growth restriction (FGR) and abnormal renewal of STB, and maternal obesity is a major risk factor for PE. Here we test the hypothesis that STB TauT activity is reduced in maternal obesity and PE compared to normal pregnancy.
STB TauT activity, measured in fragments of placental tissue, was negatively related to maternal BMI over the range 18–46 kg/m2 in both the first trimester (7–12 weeks gestation) and at term (p < 0.01; linear regression). Neither TauT activity nor expression in the first trimester differed to normal pregnancy at term. STB TauT activity was significantly lower in PE than normal pregnancy (p < 0.01). Neuropeptide Y (NPY), a protein kinase C (PKC) activator which is elevated in PE and obesity, reduced STB TauT activity by 20% (50 pM–50 nM: 2 h) (p < 0.03). Activation of PKC by phorbol 12-myristate-13-acetate (1 μM) reduced TauT activity by 18% (p < 0.05). As TauT activity is inhibited by phosphorylation, we propose that NPY activates PKC in the STB which phosphorylates TauT in PE and maternal obesity.
Reduced TauT activity could contribute to dysregulated renewal of STB and FGR that are common to PE and maternal obesity.
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Abbreviations
- TauT:
-
Taurine transporter
- STB:
-
Syncytiotrophoblast
- MVM:
-
Microvillous membrane
- BM:
-
Basal membrane
- PE:
-
Pre-eclampsia
- FGR:
-
Fetal growth restriction
- BMI:
-
Body mass index
- NPY:
-
Neuropeptide Y
- PKC:
-
Protein kinase C
- PMA:
-
Phorbol12-myristate-13-acetate
- QPCR:
-
Quantitative polymerase chain reaction
References
Baltazi M, Katsiki N et al (2011) Plasma neuropeptide Y (NPY) and alpha-melanocyte stimulating hormone (a-MSH) levels in patients with or without hypertension and/or obesity: a pilot study. Am J Cardiovasc Dis 1(1):48–59
Barker DJ (1999) Fetal origins of cardiovascular disease. Ann Med 31(Suppl 1):3–6
Calkins K, Devaskar SU (2011) “Fetal origins of adult disease.” Curr Probl Pediatr Adolesc Health Care 41(6): 158–176.
CESDI (1998). “Confidential enquiry into stillbirths and deaths in infancy. 5th Annual report.” Maternal and Child Health Consortium.
Cetin I, Corbetta C et al (1990) Umbilical amino acid concentrations in normal and growth-retarded fetuses sampled in utero by cordocentesis. Am J Obstet Gynecol 162(1):253–261
Challier JC, Basu S et al (2008) Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta. Placenta 29(3):274–281
Champion EE, Mann SJ et al (2004) System beta and system A amino acid transporters in the feline endotheliochorial placenta. Am J Physiol Regul Integr Comp Physiol 287(6):R1369–R1379
Crocker IP, Cooper S et al (2003) Differences in apoptotic susceptibility of cytotrophoblasts and syncytiotrophoblasts in normal pregnancy to those complicated with preeclampsia and intrauterine growth restriction. Am J Pathol 162(2):637–643
Desforges M, Lacey HA et al (2006) SNAT4 isoform of system A amino acid transporter is expressed in human placenta. Am J Physiol Cell Physiol 290(1):C305–C312
Desforges M, Sibley CP et al (2010) Reduced system β transporter activity in primary cytotrophoblast cells increases susceptibility to apoptotic stimuli. Reprod Sci 17:317A
Di Giulio AM, Carelli S et al (2004) Plasma amino acid concentrations throughout normal pregnancy and early stages of intrauterine growth restricted pregnancy. J Matern Fetal Neonatal Med 15(6):356–362
Economides DL, Nicolaides KH et al (1989) Plasma amino acids in appropriate- and small-for-gestational-age fetuses. Am J Obstet Gynecol 161(5):1219–1227
Evans RW, Powers RW et al (2003) Maternal and fetal amino acid concentrations and fetal outcomes during pre-eclampsia. Reproduction 125(6):785–790
Gaull G, Sturman JA et al (1972) Development of mammalian sulfur metabolism: absence of cystathionase in human fetal tissues. Pediatr Res 6(6):538–547
Ghisolfi J, Berrebi A et al (1989) Placental taurine and low birth weight infants. Biol Neonate 56(4):181–185
Greenwood SL, Sibley CP (2006) In vitro methods for studying human placental amino acid transport placental villous fragments. Methods Mol Med 122:253–264
Han X, Budreau AM et al (2000) The taurine transporter gene and its role in renal development. Amino Acids 19(3–4):499–507
Han X, Patters AB et al (2006) The taurine transporter: mechanisms of regulation. Acta Physiol (Oxf) 187(1–2):61–73
Heazell AE, Crocker IP (2008) Live and let die—regulation of villous trophoblast apoptosis in normal and abnormal pregnancies. Placenta 29(9):772–783
Heller-Stilb B, van Roeyen C et al (2002) Disruption of the taurine transporter gene (taut) leads to retinal degeneration in mice. FASEB J 16(2):231–233
Heslehurst N, Rankin J et al (2010) A nationally representative study of maternal obesity in England, UK: trends in incidence and demographic inequalities in 619 323 births, 1989–2007. Int J Obes (Lond) 34(3):420–428
Hibbard B, Milner D (1994) Reports on confidential enquiries into maternal deaths: an audit of previous recommendations. Health Trends 26(1):26–28
Higgins L, Greenwood SL et al (2011) Obesity and the placenta: A consideration of nutrient exchange mechanisms in relation to aberrant fetal growth. Placenta 32(1):1–7
Hirst C, Greenwood SL et al (2012) Reduced Placental Taurine Transport in Pre-eclampsia. Reprod Sci 19:377A
Huppertz B, Kadyrov M et al (2006) Apoptosis and its role in the trophoblast. Am J Obstet Gynecol 195(1):29–39
Jayanthi LD, Ramamoorthy S et al (1995) Substrate-specific regulation of the taurine transporter in human placental choriocarcinoma cells (JAR). Biochim Biophys Acta 1235(2):351–360
Khatun S, Kanayama N et al (2000) Increased concentrations of plasma neuropeptide Y in patients with eclampsia and preeclampsia. Am J Obstet Gynecol 182(4):896–900
Kulanthaivel P, Cool DR et al (1991) Transport of taurine and its regulation by protein kinase C in the JAR human placental choriocarcinoma cell line. Biochem J 277(Pt 1):53–58
Lacey HA, Nolan T et al (2005) Gestational profile of Na+/H + exchanger and Cl-/HCO3- anion exchanger mRNA expression in placenta using real-time QPCR. Placenta 26(1):93–98
Mbah AK, Kornosky JL et al (2010) Super-obesity and risk for early and late pre-eclampsia. BJOG 117(8):997–1004
McCormick MC (1985) The contribution of low birth weight to infant mortality and childhood morbidity. N Engl J Med 312(2):82–90
Nohr EA, Bech BH et al (2005) Prepregnancy obesity and fetal death: a study within the Danish National Birth Cohort. Obstet Gynecol 106(2):250–259
Norberg S, Powell TL et al (1998) Intrauterine growth restriction is associated with a reduced activity of placental taurine transporters. Pediatr Res 44(2):233–238
Parsons L, Greenwood SL et al (2009) The Effect of Reduced System Beta Transporter Activity on Cytotrophoblast Cell Differentiation in Vitro. Placenta 30:A83
Petraglia F, Coukos G et al (1989) Plasma and amniotic fluid immunoreactive neuropeptide-Y level changes during pregnancy, labor, and at parturition. J Clin Endocrinol Metab 69(2):324–328
Philipps AF, Holzman IR et al (1978) Tissue concentrations of free amino acids in term human placentas. Am J Obstet Gynecol 131(8):881–887
Ramamoorthy S, Del Monte MA et al (1994) Molecular identity and calmodulin-mediated regulation of the taurine transporter in a human retinal pigment epithelial cell line. Curr Eye Res 13(7):523–529
Roberts JM, Gammill HS (2005) Preeclampsia: recent insights. Hypertension 46(6):1243–1249
Robidoux J, Simoneau L et al (1998) Human syncytiotrophoblast NPY receptors are located on BBM and activate PLC-to-PKC axis. Am J Physiol 274(3 Pt 1):E502–E509
Roos S, Powell TL et al (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
Ruzycky AL, Jansson T et al (1996) Differential expression of protein kinase C isoforms in the human placenta. Placenta 17(7):461–469
Shennan DB, McNeillie SA (1995) Volume-activated amino acid efflux from term human placental tissue: stimulation of efflux via a pathway sensitive to anion transport inhibitors. Placenta 16(3):297–308
Sturman JA (1988) Taurine in development. J Nutr 118(10):1169–1176
Tertrin-Clary C, Chenut MC et al (1990) Isolation and characterization of protein kinase C from human placenta. Placenta 11(1):27–33
Tosun M, Celik H et al (2010) Maternal and umbilical serum levels of interleukin-6, interleukin-8, and tumor necrosis factor-alpha in normal pregnancies and in pregnancies complicated by preeclampsia. J Matern Fetal Neonatal Med 23(8):880–886
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
Zhang M, Bi LF et al (2004) Beneficial effects of taurine on serum lipids in overweight or obese non-diabetic subjects. Amino Acids 26(3):267–271
Acknowledgements
The authors thank the midwives and nursing staff of St. Mary’s Hospital for their assistance in obtaining placentas. The research was funded by The Wellcome Trust, Action Medical Research, and Tommy’s (Let’s Talk Baby).
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Desforges, M. et al. (2013). Reduced Placental Taurine Transporter (TauT) Activity in Pregnancies Complicated by Pre-eclampsia and Maternal Obesity. In: El Idrissi, A., L'Amoreaux, W. (eds) Taurine 8. Advances in Experimental Medicine and Biology, vol 776. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6093-0_9
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DOI: https://doi.org/10.1007/978-1-4614-6093-0_9
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