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      Maternal–Fetal Nutrient Transport in Pregnancy Pathologies: The Role of the Placenta

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          Abstract

          Appropriate in utero growth is essential for offspring development and is a critical contributor to long-term health. Fetal growth is largely dictated by the availability of nutrients in maternal circulation and the ability of these nutrients to be transported into fetal circulation via the placenta. Substrate flux across placental gradients is dependent on the accessibility and activity of nutrient-specific transporters. Changes in the expression and activity of these transporters is implicated in cases of restricted and excessive fetal growth, and may represent a control mechanism by which fetal growth rate attempts to match availability of nutrients in maternal circulation. This review provides an overview of placenta nutrient transport with an emphasis on macro-nutrient transporters. It highlights the changes in expression and activity of these transporters associated with common pregnancy pathologies, including intrauterine growth restriction, macrosomia, diabetes and obesity, as well as the potential impact of maternal diet. Molecular signaling pathways linking maternal nutrient availability and placenta nutrient transport are discussed. How sexual dimorphism affects fetal growth strategies and the placenta’s response to an altered intrauterine environment is considered. Further knowledge in this area may be the first step in the development of targeted interventions to help optimize fetal growth.

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          Most cited references137

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          Review: Sex and the human placenta: mediating differential strategies of fetal growth and survival.

          There are known sex specific differences in fetal and neonatal morbidity and mortality. There are also known differences in birthweight centile with males generally being larger than females at birth. These differences are generally ignored when studying obstetric complications of pregnancy and the mechanisms that confer these differences between the sexes are unknown. Current evidence suggests sex specific adaptation of the placenta may be central to the differences in fetal growth and survival. Our research examining pregnancies complicated by asthma has reported sexually dimorphic differences in fetal growth and survival with males adapting placental function to allow for continued growth in an adverse maternal environment while females reduce growth in an attempt to survive further maternal insults. We have reported sex differences in placental cytokine expression, insulin-like growth factor pathways and the placental response to cortisol in relation to the complication of asthma during pregnancy. More recently we have identified sex specific alterations in placental function in pregnancies complicated by preterm delivery which were associated with neonatal outcome and survival. We propose the sexually dimorphic differences in growth and survival of the fetus are mediated by the sex specific function of the human placenta. This review will present evidence supporting this hypothesis and will argue that to ignore the sex of the placenta is no longer sound scientific practice. Crown Copyright 2010. Published by Elsevier Ltd. All rights reserved.
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            Banting Lecture 1980. Of pregnancy and progeny.

            N Freinkel (1980)
            A profile characteristic of fuel economy in the mother during normal pregnancy has been delineated. The evidence indicates that pregnancy changes the metabolism of every class of foodstuff. The mechanisms by which the conceptus may be implicated are reviewed. The gestational interactions create a pattern of "accelerated starvation" whenever food is withheld, especially in late pregnancy, and they tend to "facilitate anabolism" when food is ingested. The consequent heightened metabolic oscillations during the shuttlings from fed to fasted state provide a basis for more aggressive therapy with exogenous insulin when endogenous insulin is lacking in pregnancy. It is emphasized that developing fetal structures may be exquisitely attuned to fine alterations in maternal fuel economy and that pregnancy complicated by diabetes may merely exaggerate these normal dependencies since maternal insulin affects all maternal fuels. The manifest changes in the offspring of mothers with even the mildest limitations in insulin reserve, i.e., gestational diabetes, attest to the sensitivity of the relationships. It is suggested that concepts of teratogenesis should be expanded to include alterations occurring subsequent to organogenesis during the differentiation and proliferation of fetal cells. Such changes could cause long-range effects upon behavioral, anthropometric, and metabolic functions. It is hypothesized that all of these could constitute expressions of fuel-mediated teratogenesis and that the potentialities should be incorporated into any evaluation of the outcome of pregnancy in gestations attended by disturbances in maternal fuel metabolism.
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              Cross-talk between AMPK and mTOR in regulating energy balance.

              Energy balance is maintained by a complex homeostatic system involving some signaling pathways and "nutrient sensors" in multiple tissues and organs. Any defect associated with the pathways can lead to metabolic disorders including obesity, type 2 diabetes, and the metabolic syndrome. The 5'-adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) appear to play a significant role in the intermediary metabolism of these diseases. AMPK is involved in the fundamental regulation of energy balance at the whole body level by responding to hormonal and nutrient signals in the central nervous system and peripheral tissues that modulate food intake and energy expenditure. Mammalian target of rapamycin (mTOR),is one of the downstream targets of AMPK functions as an intracellular nutrient sensor to control protein synthesis, cell growth, and metabolism. Recent research demonstrated the possible interplay between mTOR and AMPK signaling pathways. In this review, we will present current knowledge of AMPK and mTOR pathways in regulating energy balance and demonstrate the convergence between these two pathways.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                12 September 2014
                September 2014
                : 15
                : 9
                : 16153-16185
                Affiliations
                [1 ]Healthy Active Living and Obesity Research Group, Children’s Hospital of Eastern Ontario Research Institute, 401 Smyth Rd., Ottawa, ON K1H 8L1, Canada; E-Mail: kebrett123@ 123456gmail.com
                [2 ]Faculty of Health Sciences, School of Human Kinetics, University of Ottawa, 75 Laurier Avenue East, Ottawa, ON K1N 6N5, Canada
                [3 ]Division of Maternal–Fetal Medicine, Obstetrics and Gynecology, the Ottawa Hospital, 501 Smyth Rd., Ottawa, ON K1H 8L6, Canada; E-Mail: zach.ferraro@ 123456gmail.com (Z.M.F.)
                [4 ]Ottawa Hospital Research Institute, Cancer Centre, 501 Smyth Rd., Ottawa, ON K1H 8L6, Canada; E-Mail: jyockell@ 123456ohri.ca
                [5 ]Chronic Disease Program, Ottawa Hospital Research Institute, 501 Smyth Rd., Ottawa, ON K1H 8L6, Canada
                [6 ]Faculty of Medicine, Pediatrics, University of Ottawa, 5 Laurier Avenue East, Ottawa, ON K1N 6N5, Canada
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: kadamo@ 123456cheo.on.ca ; Tel.: +1-613-737-7600 (ext. 4190); Fax: +1-613-738-4800.
                Article
                ijms-15-16153
                10.3390/ijms150916153
                4200776
                25222554
                4371c47e-f683-4cbe-92b7-fdd77c523f96
                © 2014 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 28 July 2014
                : 03 September 2014
                : 04 September 2014
                Categories
                Review

                Molecular biology
                placental transport,pregnancy,maternal,glucose,amino acids,fatty acids,fetal growth
                Molecular biology
                placental transport, pregnancy, maternal, glucose, amino acids, fatty acids, fetal growth

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