Amino Acid Interconversions in the Fetal-Placental Unit: The Animal Model and Human Studies In Vivo

Cetin, Irene

doi:10.1203/00006450-200102000-00004

Cited by 103 publications

(49 citation statements)

References 38 publications

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“…The placenta concentrates folate in the intervillous space (Guigliani et al 1985a, 1985b, Cetin 2001, Camelo et al 2004. Folate receptors accumulate 5-CH 3 THF, the principal circulating form of folate, at the brush border of the syncytiotrophoblast and mediate the transport of folate compounds into the syncytiotrophoblast by endocytosis (Suh et al 2001, Van der Put et al 2001, Solanky et al 2010.…”

Section: Discussionmentioning

confidence: 99%

Placental markers of folate-related metabolism in preeclampsia

Mislanova¹,

Martsenyuk²,

Huppertz³

et al. 2011

Reproduction

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The etiology and degree of clinical symptoms of preeclampsia depend on genotypic and phenotypic maternal and trophoblast factors, and elevated levels of plasma homocysteine (Hcy) are one of the pathogenetic factors of preeclampsia. To assess the impact of the folate-related metabolism, we characterized the indices of this metabolism in 40 samples from uncomplicated term placentas and 28 samples from preeclamptic pregnancies by quantifying the total content of folate, methionine (Met), Hcy and related cysteine, and glutathione (GSH) in compliance with the 677 C/T genotype of methylene tetrahydrofolate reductase (MTHFR). The prevalence of MTHFR genotypes was not significantly different between the two groups. The polymorphism of MTHFR was not unambiguously connected with the content of total placental Met, Hcy and related cysteine, and GSH either in uncomplicated or in complicated pregnancies. By contrast, the combination of the heterozygous MTHFR genotype with folate deficiency in the samples from preeclamptic pregnancies was characterized by a statistically significant decrease in the Met content, a trend toward increased Hcy levels and a tight association between metabolically directly and indirectly related compounds, e.g. positive relation between Hcy versus cysteine and folate versus GSH and negative relation between folate versus Hcy and both Hcy and cysteine versus GSH. We demonstrated the expression of cystathionine-b-synthase (CBS) in human placenta at term by RT-PCR and western blot analysis, for the first time, and confirmed its catalytic activity and the accumulation of cysteine and CBS in placental explants cultivated in the presence of elevated Hcy concentrations. We suggest that disturbance in placental folate-related metabolism may be one of the pathogenetic factors in preeclampsia.

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Section: Discussionmentioning

confidence: 99%

Placental markers of folate-related metabolism in preeclampsia

Mislanova¹,

Martsenyuk²,

Huppertz³

et al. 2011

Reproduction

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“…Human in vivo studies with stable isotopes have shown delivery of neutral amino acids to the fetus in normal pregnancy is only just sufficient to meet requirements (Cetin, 2001), and in FGR maternofetal 13 C-leucine transfer is reduced (Marconi et al, 1999). Such findings provide the rationale for studying placental amino acid transport systems in relation to FGR.…”

Section: Placental System a And Fetal Growth Restrictionmentioning

confidence: 99%

Placental nutrient supply and fetal growth

Desforges¹,

Sibley²

2010

Int. J. Dev. Biol.

147

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This review considers mechanisms by which transfer across the placenta takes place and how the capacity of the placenta to supply nutrients relates to fetal growth and vice versa. Blood flow through both uterine and umbilical circulations of the placenta, the structural properties of the placental exchange barrier and its related diffusional permeability, and the expression and activity of a wide range of transporter proteins in the syncytiotrophoblast, the transporting epithelium of the placenta, all need to be taken into account in considering placental supply capacity. We discuss the evidence that each of these factors affects, and is affected by, fetal growth rate and consider the regulatory mechanisms involved, with a particular focus on data that has emerged from study of the system A amino acid transporter. We consider that future work will build on the considerable foundation of knowledge regarding placental transfer mechanisms, as well as the other aspects of placental structure and function, to develop new diagnostic and therapeutic strategies for pregnancy complications, such as fetal growth restriction or overgrowth.

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“…During the second half of gestation, increasing placental surface area does not match the increase in fetal size, therefore increasing amino acid transporter abundance and capacity is necessary for appropriate fetal growth. In addition, in vivo human and sheep studies have shown that many amino acids transferred to the fetus are produced in the placenta through interconversion of metabolically related amino acids [111,112].…”

Section: Placental Amino Acid Transfer and Metabolismmentioning

confidence: 99%

“…The development of techniques using isotope tracers has allowed the study of the bidirectional flow of amino acids and has improved the understanding of placental transport and metabolism of amino acids [107,[112][113][114][115]. In the human placenta, the fetal endothelial and syncytiotrophoblast layers are the only two cell layers separating maternal blood from fetal blood.…”

Section: Placental Amino Acid Transfer and Metabolismmentioning

confidence: 99%

The pregnant sheep as a model for human pregnancy

2008

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Successful outcome of human pregnancy not only impacts the quality of infant life and well-being, but considerable evidence now suggests that what happens during fetal development may well impact health and well-being into adulthood. Consequently, a thorough understanding of the developmental events that occur between conception and delivery is needed. For obvious ethical reasons, many of the questions remaining about the progression of human pregnancy can not be answered directly, necessitating the use of appropriate animal models. A variety of animal models exist for the study of both normal and compromised pregnancies, including laboratory rodents, non-human primates and domestic ruminants. While all of these animal models have merit, most suffer from the inability to repetitively sample from both the maternal and fetal side of the placenta, limiting their usefulness in the study of placental or fetal physiology under non-stressed in vivo conditions. No animal model truly recapitulates human pregnancy, yet the pregnant sheep has been used extensively to investigate maternal-fetal interactions. This is due in part to the ability to surgically place and maintain catheters in both the maternal and fetal vasculature, allowing repeated sampling from non-anesthetized pregnancies. Considerable insight has been gained on placental oxygen and nutrient transfer and utilization from use of pregnant sheep. These findings were often confirmed in human pregnancies once appropriate technologies became available. The purpose of this review is to provide an overview of human and sheep pregnancy, with emphasis placed on placental development and function as an organ of nutrient transfer.

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Amino Acid Interconversions in the Fetal-Placental Unit: The Animal Model and Human Studies In Vivo

Cited by 103 publications

References 38 publications

Placental markers of folate-related metabolism in preeclampsia

Placental markers of folate-related metabolism in preeclampsia

Placental nutrient supply and fetal growth

The pregnant sheep as a model for human pregnancy

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