The placental transfer of sugars in the sheep: studies with radioactive sugar

Alexander, D. Pauline; Andrews, Rebecca; Huggett, A. St. G.; Nixon, D. A.; Widdas, W. F.

doi:10.1113/jphysiol.1955.sp005359

Cited by 53 publications

(28 citation statements)

References 6 publications

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“…The placentas of these mammals contain little or no glycogen, i.e., less than 0.5% of that in the fetus. In contrast, mammals with endotheliochorial and hemochorial placentas (11) have fetuses in which glucose is converted to glucose-6-PO 4 that enters either the pentose phosphate pathway or the glycolytic pathway to meet the metabolic demands of the rapidly developing conceptus.Studies of pregnant ewes have revealed that (i) injection of glucose into ewes results in a rapid increase in glucose followed by a protracted increase in fructose in fetal blood; (ii) injection of glucose into the umbilical vein of the fetus increases glucose in maternal blood and hyperfructosemia in the fetus, indicating that glucose can move from conceptus vasculature to maternal blood, whereas fructose derived from glucose is not transported into maternal blood; (iii) the placenta is the site of conversion of glucose to fructose; (iv) fructose is produced continuously by the placenta independent of glucose concentration in maternal or fetal blood; and (v) the flux of glucose from the maternal to the fetal circulation can be as much as 70 mg/min in ewes made hyperglycemic (6,(12)(13)(14). These results were confirmed in studies using radiolabeled glucose to demonstrate its conversion to radiolabeled fructose by the placenta of pigs (15).…”

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confidence: 99%

Functional roles of fructose

Kim

Song

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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During the periimplantation period of pregnancy, pig blastocysts undergo morphological changes and differentiation requiring secretion and transport of nutrients (histotroph) into the uterine lumen. Of these nutrients, glucose is converted to fructose, an isomer of glucose, by conceptus trophectoderm. Although glucose is an energy source for proliferation and growth of mammalian cells, the role of fructose in uterine histotroph is unclear although it is the most abundant hexose sugar in fetal blood and fluids of ungulate mammals (e.g., cows, sheep, and pigs). In this study, we used porcine trophectoderm cells to determine that fructose increased cell proliferation, as did glucose. Western blot analyses of porcine trophectoderm cell extracts revealed that fructose increased the abundance of phosphorylated-RPS6K, -EIF4EBP1, and -RPS6 over basal levels within 30 min, and those levels remained elevated to 120 min. Phosphorylation of both RPS6K and EIF4EBP1 proteins in response to fructose was inhibited by inhibitors of both PI3K and MTOR. Further, when we investigated the inhibition of glutamine-fructose-6-phosphate transaminase 1 (GFPT1) by azaserine (an inhibitor of GFPT1) and GFPT1 siRNA, we found that MTOR-RPS6K and MTOR-EIF4EBP1 signaling in response to fructose is mediated via GFPT1 activation and the hexosamine pathway. We further demonstrated that fructose stimulates the production of hyaluronic acid via GFPT1 and the hexosamine biosynthesis pathway. Collectively, these results demonstrate critical roles for fructose that are mediated via the hexosamine biosynthesis pathway to stimulate MTOR cell signaling, proliferation of porcine trophectoderm cells, and synthesis of hyaluronic acid, a significant glycosaminoglycan in the pregnant uterus.trophoblast | glycosaminoglycans D omestic livestock species are invaluable animal models used extensively in research relevant to human and veterinary reproductive medicine as well as basic biological and biomedical sciences (1, 2). In particular, the ewe is an established animal model for studies of intrauterine growth restriction during fetal life that is a predisposition for the adult onset of metabolic disease (3). Ewes have a protracted periimplantation period of pregnancy, a relatively short period of gestation, and are well suited for metabolic studies to assess temporal and cell-specific changes in gene expression in response to various hormones, growth factors, and nutrients that are relevant to human and veterinary medicine and basic aspects of reproductive biology. Although fructose clearly is the major hexose sugar in fetal blood and fetal fluids of ungulate species such as sheep and pigs, it is largely ignored with respect to function because it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. Here we provide evidence that fructose affects multiple metabolic pathways critical to pregnancy and metabolism in multiple organ systems.Fructose is the most abundant hexose sugar in fetal fluids of ungulate mammals (4-6). Fructose ...

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Functional roles of fructose

Kim

Song

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…The methods of sugar determinations were essentially the same as those previously described (Alexander et al 1955). The values given are for whole blood and not plasma.…”

Section: Methodsmentioning

confidence: 99%

“…In an earlier paper (Alexander et al 1955) it was postulated that the new production of fructose observed by the tracer technique was balanced by placental-or foetal removal and utilization. present experiment in its initial stages indicates that the placenta can effect a removal of umbilical glucose, and since Huggett et al (1951) were unable to demonstrate back transfer of fructose to the maternal circulation it would appear that this removal is probably due to a metabolic utilization.…”

Section: P Alexander and Othersmentioning

confidence: 99%

“…In these perfusions, collections of about 60-70 mg of glucose/min were made under conditions of maternal hyperglycaemia, a value which compares with the maternal-+foetal flux measured with '4C-glucose during maternal hyperglycaemia (Alexander et al 1955).…”

Section: Elevation Of Maternal Blood Fructosementioning

confidence: 99%

“…In the detached but viable foetus the blood fructose concentration declined. This experiment formed part of their evidence that fructose was in fact produced by the placenta of sheep and not by the foetus.Alexander, Andrews, Huggett, Nixon & Widdas (1955) have demonstrated that glucose labelled with 14Carbon forms fructose even without hyperglyeaemia, and in hyperglycaemia they estimated passage of glucose from maternal to foetal circulations to be greater than 70 mg./min. The estimated production of fructose without hyperglycaemia was much smaller, being of the order of 2-7 mg/min.…”

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The placental transfer of sugars in the sheep: the influence of concentration gradient upon the rates of hexose formation as shown in umbilical perfusion of the placenta

Alexander¹,

Huggett²,

Nixon³

et al. 1955

The Journal of Physiology

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Placental perfusion via the umbilical vessels affords a means of assessing placental function without the complications of foetal metabolism. In essence the foetus is removed and the perfusing fluid circulated by a pump through that part of the placental vascular bed normally occupied by foetal blood.Huggett, described a qualitative experiment of this type in which they were able to show that the concentration of fructose in the perfusing fluid continued to rise under conditions of hyperglycaemia in the ewe. In the detached but viable foetus the blood fructose concentration declined. This experiment formed part of their evidence that fructose was in fact produced by the placenta of sheep and not by the foetus.Alexander, Andrews, Huggett, Nixon & Widdas (1955) have demonstrated that glucose labelled with 14Carbon forms fructose even without hyperglyeaemia, and in hyperglycaemia they estimated passage of glucose from maternal to foetal circulations to be greater than 70 mg./min. The estimated production of fructose without hyperglycaemia was much smaller, being of the order of 2-7 mg/min. Nevertheless, these rates were of a magnitude which might be capable of direct measurement if. the placental perfusion technique could be developed for more quantitative experiments.The purpose of the present paper is to describe experiments in which placental perfusion has been used to estimate the transfer of glucose across the placenta, the rate of production of fructose and the influence of hyperglycaemia on these placental functions.The general results indicate that whereas raised glucose concentration at one side of the placenta markedly increases the rate of glucose transfer, the rate of 24-2

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A Scientific Genealogy: Early Development of Fetal–Neonatal Research

Longo

2013

The Rise of Fetal and Neonatal Physiology

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The placental transfer of sugars in the sheep: studies with radioactive sugar

Cited by 53 publications

References 6 publications

Functional roles of fructose

Functional roles of fructose

The placental transfer of sugars in the sheep: the influence of concentration gradient upon the rates of hexose formation as shown in umbilical perfusion of the placenta

A Scientific Genealogy: Early Development of Fetal–Neonatal Research

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