Transport of amino acids through the placenta and their role

Grillo, M.A.; Lanza, A; Colombatto, Sebastiano

doi:10.1007/s00726-007-0006-5

Cited by 74 publications

(58 citation statements)

References 68 publications

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“…Glucose transport from the mother to the fetus seems to be influenced by the maternal blood glucose concentration across the placenta and is mediated by members of the facilitative glucose transporters (Baumann et al, 2002), although evidence for SLGT1-mediated Na ϩ -coupled transport in the syncytiotrophoblast has also been provided (Kevorkova et al, 2007). The maternofetal transfer of most amino acids is dependent on the coupling of secondary active amino acid transporters localized in the microvillous apical membrane of the syncytiotrophoblast (in direct contact with the maternal blood) and facilitative transporters present in the basal membrane (facing the fetal circulation) (Grillo et al, 2008). This model of nutrient vectorial flux is to some extent similar to the one described for nucleosides in (re)absorptive epithelia (intestinal and renal epithelial cells), also involving the asymmetric distribution of concentrative (CNT-type) and equilibrative (ENT-type) nucleoside transporter proteins in apical and basolateral domains, respectively, although some ENT1 expression at the apical side has also been reported (Errasti-Murugarren et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Expression and Distribution of Nucleoside Transporter Proteins in the Human Syncytiotrophoblast

Errasti-Murugarren¹,

Díaz²,

Godoy³

et al. 2011

Mol Pharmacol

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The plasma membrane distribution and related biological activity of nucleoside transporter proteins (NTs) were investigated in human syncytiotrophoblast from term placenta using a variety of approaches, including nucleoside uptake measurements into vesicles from selected plasma membrane domains, NT immunohistochemistry, and subcellular localization (basal, heavy, and light apical membranes as well as raft-enriched membranes from the apical domain). In contrast with other epithelia, in this epithelium, we have identified the high-affinity pyrimidine-preferring human concentrative nucleoside transporter (hCNT) 1 as the only hCNT-type protein expressed at both the basal and apical membranes. hCNT1 localization in lipid rafts is also dependent on its subcellular localization in the apical plasma membrane, suggesting a complex cellular and regional expression. Overall, this result favors the view that the placenta is a pyrimidine-preferring nucleoside sink from both maternal and fetal sides, and hCNT1 plays a major role in promoting pyrimidine salvage and placental growth. This finding may be of pharmacological relevance, because hCNT1 is known to interact with anticancer nucleoside-derived drugs and other molecules, such as nicotine and caffeine, for which a great variety of harmful effects on placental and fetal development, including intrauterine growth retardation, have been reported.

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Section: Discussionmentioning

confidence: 99%

Expression and Distribution of Nucleoside Transporter Proteins in the Human Syncytiotrophoblast

Errasti-Murugarren¹,

Díaz²,

Godoy³

et al. 2011

Mol Pharmacol

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“…In the human placenta, amino acid transporters belong to different families and systems (Regnault & Hay 2006, Grillo et al 2008), but little is known about their expression in uterine endometria and conceptuses. In contrast, various glucose transporters identified in preimplantation embryos provide a mechanism for glucose uptake and utilization.…”

Section: Maternal Recognition Of Pregnancymentioning

confidence: 99%

Comparative aspects of implantation

Bazer

Spencer²,

Johnson³

et al. 2009

Reproduction

345

285

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Uterine receptivity to implantation of blastocysts in mammals includes hatching from zona pellucida, precontact with uterine luminal (LE) and superficial glandular (sGE) epithelia and orientation of blastocyst, apposition between trophectoderm and uterine LE and sGE, adhesion of trophectoderm to uterine LE/sGE, and, in some species, limited or extensive invasion into the endometrial stroma and induction of decidualization of stromal cells. These peri-implantation events are prerequisites for pregnancy recognition signaling, implantation, and placentation required for fetal-placental growth and development through the remainder of pregnancy. Although there is a range of strategies for implantation in mammals, a common feature is the requirement for progesterone (P 4 ) to downregulate expression of its receptors in uterine epithelia and P 4 prior to implantation events. P 4 then mediates its effects via growth factors expressed by stromal cells in most species; however, uterine luminal epithelium may express a growth factor in response to P 4 and/or estrogens in species with a true epitheliochorial placenta. There is also compelling evidence that uterine receptivity to implantation involves temporal and cell-specific expression of interferon (IFN)-stimulated genes that may be induced directly by an IFN or induced by P 4 and stimulated by an IFN. These genes have many roles including nutrient transport, cellular remodeling, angiogenesis and relaxation of vascular tissues, cell proliferation and migration, establishment of an antiviral state, and protection of conceptus tissues from challenges by the maternal immune cells.

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“…Regarding amino acids and monoamines, 17 mammalian transport systems for amino acids have been functionally identified in the human placenta [119,120] . The interaction of xenobiotics with amino acid transport systems in the syncytiotrophoblast may result in a deficit in the transport of amino acids across the placenta.…”

Section: Protection Against Drugs and Toxinsmentioning

confidence: 99%

Excretion of biliary compounds during intrauterine life

Macı́as¹,

Marin²,

Serrano³

2009

WJG

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In adults, the hepatobiliary system, together with the kidney, constitute the main routes for the elimination of several endogenous and xenobiotic compounds into bile and urine, respectively. However, during intrauterine life the biliary route of excretion for cholephilic compounds, such as bile acids and biliary pigments, is very poor. Although very early in pregnancy the fetal liver produces bile acids, bilirubin and biliverdin, these compounds cannot be efficiently eliminated by the fetal hepatobiliary system, owing to the immaturity of the excretory machinery in the fetal liver. Therefore, the potentially harmful accumulation of cholephilic compounds in the fetus is prevented by their elimination across the placenta. Owing to the presence of detoxifying enzymes and specific transport systems at different locations of the placental barrier, such as the endothelial cells of chorionic vessels and trophoblast cells, this organ plays an important role in the hepatobiliary-like function during intrauterine life. The relevance of this excretory function in normal fetal physiology is evident in situations where high concentrations of biliary compounds are accumulated in the mother. This may result in oxidative stress and apoptosis, mainly in the placenta and fetal liver, which might affect normal fetal development and challenge the fate of the pregnancy. The present article reviews current knowledge of the mechanisms underlying the hepatobiliary function of the fetal-placental unit and the repercussions of several pathological conditions on this tandem.

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Transport of amino acids through the placenta and their role

Cited by 74 publications

References 68 publications

Expression and Distribution of Nucleoside Transporter Proteins in the Human Syncytiotrophoblast

Expression and Distribution of Nucleoside Transporter Proteins in the Human Syncytiotrophoblast

Comparative aspects of implantation

Excretion of biliary compounds during intrauterine life

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