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Placental transport in response to altered maternal nutrition

Published online by Cambridge University Press:  31 July 2012

F. Gaccioli
Affiliation:
Department of Obstetrics and Gynecology, Center for Pregnancy and Newborn Research, University of Texas Health Science Center, San Antonio, TX, USA
S. Lager
Affiliation:
Department of Obstetrics and Gynecology, Center for Pregnancy and Newborn Research, University of Texas Health Science Center, San Antonio, TX, USA
T. L. Powell
Affiliation:
Department of Obstetrics and Gynecology, Center for Pregnancy and Newborn Research, University of Texas Health Science Center, San Antonio, TX, USA
T. Jansson*
Affiliation:
Department of Obstetrics and Gynecology, Center for Pregnancy and Newborn Research, University of Texas Health Science Center, San Antonio, TX, USA
*
*Address for correspondence: Dr T. Jansson, Department of Obstetrics and Gynecology, Center for Pregnancy and Newborn Research, University of Texas Health Science Center, Mail Code 7836, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. (Email jansson@uthscsa.edu)

Abstract

The mechanisms linking maternal nutrition to fetal growth and programming of adult disease remain to be fully established. We review data on changes in placental transport in response to altered maternal nutrition, including compromized utero-placental blood flow. In human intrauterine growth restriction and in most animal models involving maternal undernutrition or restricted placental blood flow, the activity of placental transporters, in particular for amino acids, is decreased in late pregnancy. The effect of maternal overnutrition on placental transport remains largely unexplored. However, some, but not all, studies in women with diabetes giving birth to large babies indicate an upregulation of placental transporters for amino acids, glucose and fatty acids. These data support the concept that the placenta responds to maternal nutritional cues by altering placental function to match fetal growth to the ability of the maternal supply line to allocate resources to the fetus. On the other hand, some findings in humans and mice suggest that placental transporters are regulated in response to fetal demand signals. These observations are consistent with the idea that fetal signals regulate placental function to compensate for changes in nutrient availability. We propose that the placenta integrates maternal and fetal nutritional cues with information from intrinsic nutrient sensors. Together, these signals regulate placental growth and nutrient transport to balance fetal demand with the ability of the mother to support pregnancy. Thus, the placenta plays a critical role in modulating maternal–fetal resource allocation, thereby affecting fetal growth and the long-term health of the offspring.

Type
Review
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012 

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References

1.Gluckman, PD, Hanson, MA, Cooper, C, Thornburg, KL. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med. 2008; 359, 6173.Google Scholar
2.Symonds, ME, Sebert, SP, Hyatt, MA, Budge, H. Nutritional programming of the metabolic syndrome. Nat Rev Endocrinol. 2009; 5, 604610.CrossRefGoogle ScholarPubMed
3.Jansson, N, Pettersson, J, Haafiz, A, et al. Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet. J Physiol. 2006; 576, 935946.Google ScholarPubMed
4.Malandro, MS, Beveridge, MJ, Kihlberg, MS, Novak, DA. Effect of low-protein diet-induced intrauterine growth retardation on rat placental amino acid transport. Am J Physiol. 1996; 271, C295C303.Google Scholar
5.Constancia, M, Hemberger, M, Hughes, J, et al. Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature. 2002; 417, 945948.Google Scholar
6.Zhu, MJ, Du, M, Hess, BW, Nathanielsz, PW, Ford, SP. Periconceptional nutrient restriction in the ewe alters MAPK/ERK1/2 and PI3K/Akt growth signaling pathways and vascularity in the placentome. Placenta. 2007; 28, 11921199.CrossRefGoogle ScholarPubMed
7.Zhu, MJ, Ma, Y, Long, NM, Du, M, Ford, SP. Maternal obesity markedly increases placental fatty acid transporter expression and fetal blood triglycerides at midgestation in the ewe. Am J Physiol Regul Integr Comp Physiol. 2010; 299, R1224R1231.CrossRefGoogle ScholarPubMed
8.Rosario, FJ, Jansson, N, Kanai, Y, et al. Maternal protein restriction in the rat inhibits placental insulin, mTOR, and STAT3 signaling and down-regulates placental amino acid transporters. Endocrinology. 2011; 152, 11191129.Google Scholar
9.Belkacemi, L, Nelson, DM, Desai, M, Ross, MG. Maternal undernutrition influences placental-fetal development. Biol Reprod. 2010; 83, 325331.CrossRefGoogle ScholarPubMed
10.Kaufmann, P, Burton, GJ. Anatomy and genesis of the placenta. In The Physiology of Reproduction (eds. Knobil E, Neill JD) 1994; pp. 441483. Raven Press: New York.Google Scholar
11.Kusinski, LC, Jones, CJ, Baker, PN, Sibley, CP, Glazier, JD. Isolation of plasma membrane vesicles from mouse placenta at term and measurement of system A and system beta amino acid transporter activity. Placenta. 2010; 31, 5359.Google Scholar
12.Burton, GJ, Kaufmann, P, Huppertz, B. Anatomy and genesis of the placenta. In Knobil and Neill's Physiology of Reproduction (ed. Neill JD), 2006; pp. 189241. Elsevier: Amsterdam.CrossRefGoogle Scholar
13.Wooding, FP, Flint, APF. Placentation. In Marshall's Physiology of Reproduction (ed. Lamming GE) 1994; pp. 233460. Chapman & Hall: London.Google Scholar
14.Carter, AM. Evolution of factors affecting placental oxygen transfer. Placenta. 2009; 30(Suppl. A), S19S25.Google Scholar
15.Jansson, T, Powell, TL. Placental function in maternofetal exchange. In Fetal Medicine: Basic Science and Clinical Practice (eds. Rodeck CH, Whittle MJ), 2009; pp. 97109. Churchill Livingstone Elsevier: London.Google Scholar
16.Sibley, CP, Boyd, RDH. Mechanisms of transfer across the human placenta. In Fetal and Neonatal Physiology (eds. Polin RA, Fox WW), 1998; pp. 7789. WB Saunders Co.: Philadelphia.Google Scholar
17.Sibley, CP, Boyd, RDH. Control of transfer across the mature placenta. In Oxford Reviews of Reproductive Biology (ed. Clarke JR), 1988; pp. 382423. Oxford University Press: Oxford.Google Scholar
18.Atkinson, DE, Boyd, RDH, Sibley, CP. Placental transfer. In Knobil and Neill's Physiology of Reproduction (ed. Neill JD) 2006; pp. 27872846. Elsevier: Amsterdam.Google Scholar
19.Jansson, T, Powell, TL. Human placental transport in altered fetal growth: Does the placenta function as a nutrient sensor? – A review. Placenta. 2006; 27(Suppl.), 9197.Google Scholar
20.Sibley, CP, Brownbill, P, Dilworth, M, Glazier, JD. Review: adaptation in placental nutrient supply to meet fetal growth demand: implications for programming. Placenta. 2010; 31(Suppl.), S70S74.Google Scholar
21.Constancia, M, Angiolini, E, Sandovici, I, et al. Adaptation of nutrient supply to fetal demand in the mouse involves interaction between the Igf2 gene and placental transporter systems. Proc Natl Acad Sci U S A. 2005; 102, 1921919224.Google Scholar
22.Angiolini, E, Coan, PM, Sandovici, I, et al. Developmental adaptations to increased fetal nutrient demand in mouse genetic models of Igf2-mediated overgrowth. FASEB J. 2011; 25, 17371745.Google Scholar
23.Lumey, LH. Compensatory placental growth after restricted maternal nutrition in early pregnancy. Placenta. 1998; 19, 105111.Google ScholarPubMed
24.Sibley, CP, Turner, MA, Cetin, I, et al. Placental phenotypes of intrauterine growth. Pediatr Res. 2005; 58, 827832.CrossRefGoogle ScholarPubMed
25.Sibley, C, D′Souza, S, Glazier, J, Greenwood, S. Mechanisms of solute transfer across the human placenta: effects of intrauterine growth restriction. Fetal Matern Med Rev. 1998; 10, 197206.CrossRefGoogle Scholar
26.Cetin, I, Alvino, G. Intrauterine growth restriction: implications for placental metabolism and transport. A review. Placenta. 2009; 30(Suppl. A), S77S82.Google Scholar
27.Dicke, JM, Verges, DK. Neutral amino acid uptake by microvillous and basal plasma membrane vesicles from appropriate- and small-for- gestational age human pregnancies. J Matern Fetal Med. 1994; 3, 246250.CrossRefGoogle Scholar
28.Jansson, T, Ylvén, K, Wennergren, M, Powell, TL. Glucose transport and system A activity in syncytiotrophoblast microvillous and basal membranes in intrauterine growth restriction. Placenta. 2002; 23, 386391.CrossRefGoogle ScholarPubMed
29.Glazier, JD, Cetin, I, Perugino, G, et al. Association between the activity of the system a amino acid transporter in the microvillous plasma membrane of the human placenta and severity of fetal compromise in intrauterine growth restriction. Pediatr Res. 1997; 42, 514519.Google Scholar
30.Mahendran, D, Donnai, P, Glazier, JD, et al. Amino acid (System A) transporter activity in microvillous membrane vesicles from the placentas of appropriate and small for gestational age babies. Pediatr Res. 1993; 34, 661665.Google Scholar
31.Jansson, T, Scholtbach, V, Powell, TL. Placental transport of leucine and lysine is reduced in intrauterine growth restriction. Pediatr Res. 1998; 44, 532537.Google Scholar
32.Norberg, S, Powell, TL, Jansson, T. Intrauterine growth restriction is associated with a reduced activity of placental taurine transporters. Pediatr Res. 1998; 44, 233238.CrossRefGoogle ScholarPubMed
33.Roos, S, Powell, TL, Jansson, T. Human placental taurine transporter in uncomplicated and IUGR pregnancies: cellular localization, protein expression, and regulation. Am J Physiol Regul Integr Comp Physiol. 2004; 287, R886R893.Google Scholar
34.Ayuk, PTY, Theophanous, D, D'Souza, SW, Sibley, CP, Glazier, JD. l-Arginine transport by the microvillous plasma membrane of the syncytiotrophoblast from human placenta in relation to nitric oxide production: effects of gestation, preeclampsia, and intrauterine growth restriction. J Clin Endocrinol Metab. 2002; 87, 747751.Google Scholar
35.Jansson, T, Wennergren, M, Illsley, NP. Glucose transporter protein expression in human placenta throughout gestation and in intrauterine growth retardation. J Clin Endocrinol Metab. 1993; 77, 15541562.Google Scholar
36.Magnusson, AL, Waterman, IJ, Wennergren, M, Jansson, T, Powell, TL. Triglyceride hydrolase activities and expression of fatty acid binding proteins in human placenta in pregnancies complicated by IUGR and diabetes. J Clin Endocrinol Metab. 2004; 89, 46074614.CrossRefGoogle ScholarPubMed
37.Strid, H, Bucht, E, Jansson, T, Wennergren, M, Powell, T. ATP-dependent Ca2+ transport across basal membrane of human syncytiotrophoblast in pregnancies complicated by diabetes or intrauterine growth restriction. Placenta. 2003; 24, 445452.CrossRefGoogle ScholarPubMed
38.Johansson, M, Jansson, T, Glazier, JD, Powell, TL. Activity and expression of the Na+/H+ exchanger is reduced in syncytiotrophoblast microvillous plasma membranes isolated from preterm intrauterine growth restriction pregnancies. J Clin Endocrinol Metab. 2002; 87, 56865694.CrossRefGoogle ScholarPubMed
39.Settle, P, Sibley, CP, Doughty, IM, et al. Placental lactate transporter activity and expression in intrauterine growth restriction. J Soc Gynecol Investig. 2006; 13, 357363.Google Scholar
40.Johansson, M, Karlsson, L, Wennergren, M, Jansson, T, Powell, TL. Activity and protein expression of Na+K+ ATPase are reduced in microvillous syncytiotrophoblast plasma membranes isolated from pregnancies complicated by intrauterine growth restriction. J Clin Endocrinol Metab. 2003; 88, 28312837.Google Scholar
41.Economides, DL, Nicolaides, KH. Blood glucose and oxygen tension in small-for-gestational-age fetuses. Am J Obstet Gynecol. 1989; 160, 120126.Google Scholar
42.Zamudio, S, Torricos, T, Fik, E, et al. Hypoglycemia and the origin of hypoxia-induced reduction in human fetal growth. PLoS One. 2010; 5, e8551.Google Scholar
43.Mackenzie, B, Erickson, JD. Sodium-coupled neutral amino acid (System N/A) transporters of the SLC38 gene family. Pflugers Arch. 2004; 447, 784795.CrossRefGoogle ScholarPubMed
44.Shibata, E, Hubel, CA, Powers, RW, et al. Placental System A amino acid transport is reduced in pregnancies complicated with small for gestational age (SGA) infants but not in preecalmpsia with SGA infants. Placenta. 2008; 29, 879882.Google Scholar
45.Jansson, N, Greenwood, S, Johansson, BR, Powell, TL, Jansson, T. Leptin stimulates the activity of the system A amino acid transporter in human placental villous fragments. J Clin Endocrinol Metab. 2003; 88, 12051211.Google Scholar
46.von Versen-Hoynck, F, Rajakumar, A, Parrott, MS, Powers, RW. Leptin affects system A amino acid transport activity in the human placenta: evidence for STAT3 dependent mechanisms. Placenta. 2009; 30, 361367.CrossRefGoogle ScholarPubMed
47.Tsitsiou, E, Sibley, CP, D'Souza, SW, et al. Homocysteine is transported by the microvillous plasma membrane of human placenta. J Inherit Metab Dis. 2011; 34, 5765.Google Scholar
48.Marconi, AM, Paolini, CL, Stramare, L, et al. Steady state maternal–fetal leucine enrichments in normal and intrauterine growth-restricted pregnancies. Pediatr Res. 1999; 46, 114119.CrossRefGoogle ScholarPubMed
49.Paolini, CL, Marconi, AM, Ronzoni, S, et al. Placental transport of leucine, phenylalanine, glycine, and proline in intrauterine growth-restricted pregnancies. J Clin Endocrinol Metab. 2001; 86, 54275432.Google Scholar
50.Cetin, I, Corbetta, C, Sereni, LP, et al. Umbilical amino acid concentrations in normal and growth-retarded fetuses sampled in utero by cordocentesis. Am J Obstet Gynecol. 1990; 162, 253261.Google Scholar
51.Cetin, I, Marconi, AM, Bozzetti, P, et al. Umbilical amino acid concentrations in appropriate and small for gestational age infants: a biochemical difference present in utero. Am J Obstet Gynecol. 1988; 158, 120126.Google Scholar
52.Economides, DL, Nicolaides, KH, Gahl, WA, Bernadini, I, Evans, MI. Plasma amino acids in appropriate- and small-for-gestational-age fetuses. Am J Obstet Gynecol. 1989; 161, 12191227.Google Scholar
53.Cetin, I, Giovannini, N, Alvino, G, et al. Intrauterine growth restriction is associated with changes in polyunsaturated fatty acid fetal–maternal relationships. Pediatr Res. 2002; 52, 750755.Google Scholar
54.Heasman, L, Clarke, L, Firth, K, Stephenson, T, Symonds, ME. Influence of restricted maternal nutrition in early to mid gestation on placental and fetal development at term in sheep. Pediatr Res. 1998; 44, 546551.Google Scholar
55.Langley-Evans, S, Gardner, D, Jackson, A. Association of disproportionate growth of fetal rats in late gestation with raised systolic blood pressure in later life. J Reprod Fertil. 1996; 106, 307312.Google Scholar
56.Schlabritz-Loutsevitch, N, Ballesteros, B, Dudley, C, et al. Moderate maternal nutrient restriction, but not glucocorticoid administration, leads to placental morphological changes in the baboon (Papio sp). Placenta. 2007; 28, 783793.Google Scholar
57.Dwyer, CM, Madgwick, AJ, Crook, AR, Stickland, NC. The effect of maternal undernutrition on the growth and development of the guinea pig placenta. J Dev Physiol. 1992; 18, 295302.Google Scholar
58.Belkacemi, L, Chen, CH, Ross, MG, Desai, M. Increased placental apoptosis in maternal food restricted gestations: role of the Fas pathway. Placenta. 2009; 30, 739751.Google Scholar
59.Kavitha, JV, Nathanielsz, PW, McDonald, TJ, et al. Down regulation of placental amino acid and glucose transporters in response to maternal nutrient restriction in the baboon. Reprod Sci. 2012; 19(Suppl.), 378A (Abstract).Google Scholar
60.Rosso, P. Maternal-fetal exchange during protein malnutrition in the rat. Placental transfer of glucose and a nonmetabolizable glucose analog. J Nutr. 1977; 107, 2000620010.Google Scholar
61.Rosso, P. Maternal-fetal exchange during protein malnutrition in the rat. Placental transfer of alpha-amino isobutyric acid. J Nutr. 1977; 107, 20022005.Google Scholar
62.Rosso, P. Maternal malnutrition and placental transfer of alpha-aminoisobutyric acid in the rat. Science. 1975; 187, 648650.Google Scholar
63.Varma, DR, Ramakrishnan, R. Effects of protein-calorie malnutrition on transplacental kinetics of aminoisobutyric acid in rats. Placenta. 1991; 12, 277284.Google Scholar
64.Ahokas, RA, Lahaye, EB, Anderson, GD, Lipshitz, J. Effect of maternal dietary restriction on fetal growth and placental transfer of alpha-amino isobutyric acid in rats. J Nutr. 1981; 111, 20522058.CrossRefGoogle ScholarPubMed
65.Belkacemi, L, Jelks, A, Chen, CH, Ross, MG, Desai, M. Altered placental development in undernourished rats: role of maternal glucocorticoids. Reprod Biol Endocrinol. 2011; 9, 105.Google Scholar
66.Lesage, J, Hahn, D, Leonhardt, M, et al. Maternal undernutrition during late gestation-induced intrauterine growth restriction in the rat is associated with impaired placental GLUT3 expression, but does not correlate with endogenous corticosterone levels. J Endocrinol. 2002; 174, 3743.Google Scholar
67.Sferruzzi-Perri, AN, Vaughan, OR, Coan, PM, et al. Placental-specific Igf2 deficiency alters developmental adaptations to undernutrition in mice. Endocrinology. 2011; 152, 32023212.Google Scholar
68.Coan, PM, Vaughan, OR, Sekita, Y, et al. Adaptations in placental phenotype support fetal growth during undernutrition of pregnant mice. J Physiol. 2010; 588, 527538.Google Scholar
69.Coan, PM, Vaughan, OR, McCarthy, J, et al. Dietary composition programmes placental phenotype in mice. J Physiol. 2011; 589, 36593670.Google Scholar
70.Miller, J, Turan, S, Baschat, AA. Fetal growth restriction. Semin Perinatol. 2008; 32, 274280.CrossRefGoogle ScholarPubMed
71.Nitzan, M, Orloff, S, Schulman, JD. Placental transfer of analogs of glucose and amino acids in experimental intrauterine growth retardation. Pediatr Res. 1979; 13, 100103.Google Scholar
72.Glazier, JD, Sibley, CP, Carter, AM. Effect of fetal growth restriction on system A amino acid transporter activity in the maternal facing plasma membrane of rat syncytiotrophoblast. Pediatr Res. 1996; 40, 325329.Google Scholar
73.Reid, GJ, Lane, RH, Flozak, AS, Simmons, RA. Placental expression of glucose transporter proteins 1 and 3 in growth-restricted fetal rats. Am J Obstet Gynecol. 1999; 180, 10171023.Google Scholar
74.Jansson, T, Persson, E. Placental transfer of glucose and aminoacids in intrauterine growth retardation: studies with substrate analogs in the awake guinea pig. Pediatr Res. 1990; 28, 203208.Google Scholar
75.Saintonge, J, Rosso, P. Placental blood flow and transfer of nutrient analogs in large, average, and small guinea pig littermates. Pediatr Res. 1981; 15, 152156.Google Scholar
76.Coan, PM, Angiolini, E, Sandovici, I, et al. Adaptations in placental nutrient transfer capacity to meet fetal growth demands depend on placental size in mice. J Physiol. 2008; 586, 45674576.Google Scholar
77.Barry, JS, Rozance, PJ, Anthony, RV. An animal model of placental insufficiency-induced intrauterine growth restriction. Semin Perinatol. 2008; 32, 225230.Google Scholar
78.Thureen, PJ, Trembler, KA, Meschia, G, Makowski, EL, Wilkening, RB. Placental glucose transport in heat-induced fetal growth retardation. Am J Physiol. 1992; 263, R578R585.Google Scholar
79.Ross, JC, Fennessey, PV, Wilkening, RB, Battaglia, FC, Meschia, G. Placental transport and fetal utilization of leucine in a model of fetal growth retardation. Am J Physiol. 1996; 270, E491E503.Google Scholar
80.Anderson, AH, Fennessey, PV, Meschia, G, Wilkening, RB, Battaglia, FC. Placental transport of threonine and its utilization in the normal and growth-restricted fetus. Am J Physiol. 1997; 272, E892E900.Google Scholar
81.de Vrijer, B, Regnault, TR, Wilkening, RB, Meschia, G, Battaglia, FC. Placental uptake and transport of ACP, a neutral nonmetabolizable amino acid, in an ovine model of fetal growth restriction. Am J Physiol. 2004; 287, E1114E1124.Google Scholar
82.Crowe, C, Dandekar, P, Fox, M, et al. The effects of anaemia on heart, placenta and body weight, and blood pressure in fetal and neonatal rats. J Physiol. 1995; 488, 515519.Google Scholar
83.Godfrey, KM, Barker, DJ. Maternal nutrition in relation to fetal and placental growth. Eur J Obstet Gynecol Reprod Biol. 1995; 61, 1522.Google Scholar
84.Gambling, L, Danzeisen, R, Gair, S, et al. Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro. Biochem J. 2001; 356, 883889.Google Scholar
85.Metzger, BE, Lowe, LP, Dyer, AR, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008; 358, 19912002.Google Scholar
86.Jansson, T, Ekstrand, Y, Björn, C, Wennergren, M, Powell, TL. Alterations in the activity of placental amino acid transporters in pregnancies complicated by diabetes. Diabetes. 2002; 51, 22142219.Google Scholar
87.Kuruvilla, AG, D'Souza, SW, Glazier, JD, et al. Altered activity of the system A amino acid transporter in microvillous membrane vesicles from placentas of macrosomic babies born to diabetic women. J Clin Invest. 1994; 94, 689695.Google Scholar
88.Jansson, T, Ekstrand, Y, Wennergren, M, Powell, TL. Placental glucose transport in gestational diabetes. Am J Obstet Gynecol. 2001; 184, 111116.Google Scholar
89.Jansson, T, Wennergren, M, Powell, TL. Placental glucose transport and GLUT 1 expression in insulin dependent diabetes. Am J Obstet Gynecol. 1999; 180, 163168.Google Scholar
90.Gaither, K, Quraishi, AN, Illsley, NP. Diabetes alters the expression and activity of the human placental GLUT1 glucose transporter. J Clin Endocrinol Metab. 1999; 84, 695701.Google Scholar
91.Persson, A, Johansson, M, Jansson, T, Powell, TL. Na+/K+-ATPase activity and expression in syncytiotrophoblast plasma membranes in pregnancies complicated by diabetes. Placenta. 2002; 23, 386391.Google Scholar
92.Dicke, JM, Henderson, GI. Placental amino acid uptake in normal and complicated pregnancies. Am J Med Sci. 1988; 295, 223227.Google Scholar
93.Bibee, KP, Illsley, NP, Moley, KH. Asymmetric syncytial expression of GLUT9 splice variants in human term placenta and alterations in diabetic pregnancies. Reprod Sci. 2011; 18, 2027.CrossRefGoogle ScholarPubMed
94.Osmond, DT, Nolan, CJ, King, RG, Brennecke, SP, Gude, NM. Effects of gestational diabetes on human placental glucose uptake, transfer, and utilisation. Diabetologia. 2000; 43, 576582.Google Scholar
95.Osmond, DT, King, RG, Brennecke, SP, Gude, NM. Placental glucose transport and utilisation is altered at term in insulin-treated, gestational-diabetic patients. Diabetologia. 2001; 44, 11331139.CrossRefGoogle ScholarPubMed
96.Desoye, G, Gauster, M, Wadsack, C. Placental transport in pregnancy pathologies. Am J Clin Nutr. 2011; 94(Suppl 6), 1896S1902S.Google Scholar
97.Gil-Sanchez, A, Koletzko, B, Larque, E. Current understanding of placental fatty acid transport. Curr Opin Clin Nutr Metab Care. 2012; 15, 265272.CrossRefGoogle ScholarPubMed
98.Lindegaard, MLS, Damm, P, Mathiesen, ER, Nielsen, LB. Placental triglyceride accumulation in maternal type 1 diabetes is associated with increased lipase gene expression. J Lipid Res. 2006; 47, 25812588.Google Scholar
99.Scifres, CM, Chen, B, Nelson, DM, Sadovsky, Y. Fatty acid binding protein 4 regulates intracellular lipid accumulation in human trophoblasts. J Clin Endocrinol Metab. 2011; 96, E1083E1091.Google Scholar
100.Gauster, M, Hiden, U, van Poppel, M, et al. Dysregulation of placental endothelial lipase in obese women with gestational diabetes mellitus. Diabetes. 2011; 60, 24572464.Google Scholar
101.Wijendran, V, Bendel, RB, Couch, SC, et al. Fetal erythrocyte phospholipid polyunsaturated fatty acids are altered in pregnancy complicated with gestational diabetes mellitus. Lipids. 2000; 35, 927931.Google Scholar
102.Higgins, L, Greenwood, SL, Wareing, M, Sibley, CP, Mills, TA. Obesity and the placenta: a consideration of nutrient exchange mechanisms in relation to aberrant fetal growth. Placenta. 2011; 32, 17.Google Scholar
103.Chu, SY, Kim, SY, Bish, CL. Prepregnancy obesity prevalence in the United States, 2004–2005. Matern Child Health J. 2009; 13, 614620.Google Scholar
104.Sebire, NJ, Jolly, M, Harris, JP, et al. Maternal obesity and pregnancy outcome: a study of 287,213 pregnancies in London. Int J Obes Relat Metab Disord. 2001; 25, 11751182.CrossRefGoogle Scholar
105.Baeten, JM, Bukusi, EA, Lambe, M. Pregnancy complications and outcomes among overweight and obese nulliparous women. Am J Publ Health. 2001; 91, 436440.Google Scholar
106.Ehrenberg, HM, Mercer, BM, Catalano, PM. The influence of obesity and diabetes on the prevalence of macrosomia. Am J Obstet Gynecol. 2004; 191, 964968.Google Scholar
107.Farley, DM, Choi, J, Dudley, DJ, et al. Placental amino acid transport and placental leptin resistance in pregnancies complicated by maternal obesity. Placenta. 2010; 31, 718724.Google Scholar
108.Gaccioli, F, Jansson, T, Powell, TL. Placental System A and System L amino acid transporter activity and expression in lean and overweight/obese Hispanic women. Reprod Sci. 2012; 19, 377A (Abstract).Google Scholar
109.Jansson, N, Jones, HN, Schumacher, M, et al. Altered AMPK and mTOR signaling and up-regulation of placental System A amino acid transporter activity and SNAT2 protein expression in obese women giving birth to large babies. Reprod Sci. 2010; 17, 260A (Abstract).Google Scholar
110.Dube, E, Gravel, A, Martin, C, et al. Modulation of fatty acid transport and metabolism by obesity in the human full-term placenta. Biol Reprod. 2012; May 2 [E-pub ahead of print].Google Scholar
111.Jawerbaum, A, White, V. Animal models in diabetes and pregnancy. Endocr Rev. 2010; 31, 680701.Google Scholar
112.Palacin, M, Lasuncion, MA, Martin, A, Herrera, E. Decreased uterine blood flow in the diabetic pregnant rat does not modify the augmented glucose transfer to the fetus. Biol Neonate. 1985; 48, 197203.Google Scholar
113.Eriksson, U, Jansson, L. Diabetes in pregnancy: decreased placental blood flow and disturbed fetal development in the rat. Pediatr Res. 1984; 18, 735738.Google Scholar
114.Copeland, AD Jr, Porterfield, SP. Effects of streptozotocin-induced diabetes in pregnant rats on placental transport and tissue uptake of alpha-amino-isobutyric acid. Horm Metab Res. 1987; 19, 5761.CrossRefGoogle ScholarPubMed
115.Ogura, K, Sakata, M, Yamaguchi, M, Kurachi, H, Murata, Y. High concentration of glucose decreases glucose transporter-1 expression in mouse placenta in vitro and in vivo. J Endocrinol. 1999; 160, 443452.Google Scholar
116.Devaskar, S, Devaskar, U, Schroeder, R, et al. Expression of genes involved in placental glucose uptake and transport in the nonobese diabetic mouse pregnancy. Am J Obstet Gynecol. 1994; 171, 13161323.Google Scholar
117.Boileau, P, Mrejen, C, Girard, J, Hauguel-de-Mouzon, S. Overexpression of GLUT 3 placental glucose transporter in diabetic rats. J Clin Invest. 1995; 96, 309317.Google Scholar
118.Herrera, E, Palacin, M, Martin, A, Lasuncion, M. Relationship between maternal and fetal fuels and placental glucose transfer in rats with maternal diabetes of varying severity. Diabetes. 1985; 34(Suppl 2), 4246.Google Scholar
119.Thomas, C, Lowy, C. Placental transfer and uptake of 2-deoxyglucose in control and diabetic rats. Metabolism. 1992; 41, 11991203.Google Scholar
120.Honda, M, Lowy, C, Thomas, CR. The effects of maternal diabetes on placental transfer of essential and non-essential fatty acids in the rat. Diabetes Res. 1990; 15, 4751.Google ScholarPubMed
121.Shafrir, E, Khassis, S. Maternal-fetal fat transport versus new fat synthesis in the pregnant diabetic rat. Diabetologia. 1982; 22, 111117.Google Scholar
122.Goldstein, R, Levy, E, Shafrir, E. Increased maternal-fetal transport of fat in diabetes assessed by polyunsaturated fatty acid content in fetal lipids. Biol Neonate. 1985; 47, 343349.Google Scholar
123.Li, M, Sloboda, DM, Vickers, MH. Maternal obesity and developmental programming of metabolic disorders in offspring: evidence from animal models. Exp Diabetes Res. 2011; 2011, 592408. Epub 28 September 2011.Google Scholar
124.Armitage, JA, Khan, IY, Taylor, PD, Nathanielsz, PW, Poston, L. Developmental programming of metabolic syndrome by maternal nutritional imbalance; how strong is the evidence from expermental models in animals. J Physiol. 2004; 561, 355377.Google Scholar
125.Wallace, JM, Bourke, DA, Aitken, RP, Milne, JS, Hay, WW Jr. Placental glucose transport in growth-restricted pregnancies induced by adolescent sheep. J Physiol. 2003; 547, 8594.Google Scholar
126.Frias, AE, Morgan, TK, Evans, AE, et al. Maternal high-fat diet disturbs uteroplacental hemodynamics and increases the frequency of stillbirth in a nonhuman primate model of excess nutrition. Endocrinology. 2011; 152, 24562464.Google Scholar
127.Jones, HN, Woollett, LP, Barbour, N, et al. High fat diet before and during pregnancy causes marked up-regulation of placental nutrient transport and fetal overgrowth in C57/Bl6 mice. FASEB J. 2009; 23, 271278.CrossRefGoogle ScholarPubMed
128.Rebholz, SL, Burke, KT, Yang, Q, Tso, P, Woollett, LA. Dietary fat impacts fetal growth and metabolism: uptake of chylomicron remnant core lipids by the placenta. Am J Physiol Endocrinol Metab. 2011; 301, E416E425.Google Scholar
129.Jones, HN, Powell, TL, Jansson, T. Regulation of placental nutrient transport – a review. Placenta. 2007; 28, 763774.Google Scholar
130.Lager, S, Powell, TL. Regulation of transport across the placenta. J Pregnancy. 2012 (In Press).Google Scholar
131.Longo, VD, Fontana, L. Calorie restriction and cancer prevention: metabolic and molecular mechanisms. Trends Pharmacol Sci. 2010; 31, 8998.Google Scholar
132.Holmes, R, Montemagno, R, Jones, J, et al. Fetal and maternal plasma insulin-like growth factors in pregnancies with appropriate or retarded fetal growth. Early Hum Dev. 1997; 49, 717.Google Scholar
133.Yildiz, L, Avci, B, Ingec, M. Umbilical cord and maternal blood leptin concentrations in intrauterine growth retardation. Clin Chem Lab Med. 2002; 40, 11141117.Google Scholar
134.Potau, N, Riudor, E, Ballabriga, A. Insulin receptors in human placenta in relation to fetal weight and gestational age. Pediatr Res. 1981; 15, 798802.Google Scholar
135.Laviola, L, Perrini, S, Belsanti, G, et al. Intrauterine growth restriction in humans is associated with abnormalities in placental insulin-like growth factor signaling. Endocrinology. 2005; 146, 14981505.CrossRefGoogle ScholarPubMed
136.Lea, RG, Howe, D, Hannah, LT, et al. Placental leptin in normal diabetic and fetal growth-retarded pregnancies. Mol Hum Reprod. 2000; 6, 763769.Google Scholar
137.Ramsay, JE, Ferrell, WR, Crawford, L, et al. Maternal obesity is associated with dysregulation of metabolic, vascular and inflammatory pathways. J Clin Endocrinol Metab. 2002; 87, 42314237.Google Scholar
138.Jansson, N, Nilsfelt, A, Gellerstedt, M, et al. Maternal hormones linking maternal bodymass index and dietary intake to birth weight. Am J Clin Nutr. 2008; 87, 17431749.Google Scholar
139.Lauszus, FF, Klebe, JG, Flyvbjerg, A. Macrosomia associated with maternal serum insulin-like growth factor-I and -II in diabetic pregnancy. Obstet Gynecol. 2001; 97, 734741.Google Scholar
140.Karl, PI. Insulin-like growth factor-1 stimulates amino acid uptake by the cultured human placental trophoblast. J Cell Physiol. 1995; 165, 8388.Google Scholar
141.Karl, PI, Alpy, KL, Fischer, SE. Amino acid transport by the cultured human placental trophoblast: effect of insulin on AIB transport. Am J Physiol. 1992; 262, C834C839.Google Scholar
142.Jones, HN, Jansson, T, Powell, TL. IL-6 stimulates System A amino acid transporter activity in trophoblast cells through STAT3 and increased expression of SNAT2. Am J Physiol Cell. 2009; 297, C1228C1235.Google Scholar
143.Jones, HN, Jansson, T, Powell, TL. Full length adiponectin attenuates insulin signaling and inhibits insulin-stimulated amino acid transport in human primary trophoblast cells. Diabetes. 2010; 59, 11611170.Google Scholar
144.Rosario, FJ, Schumacher, MA, Jiang, J, et al. Chronic maternal infusion of full-length adiponectin in pregnant mice down-regulates placental amino acid transporter activity and expression and decreases fetal growth. J Physiol. 2012; 590, 14951509.Google Scholar
145.Sferruzzi-Perri, AN, Owens, JA, Standen, P, et al. Early treatment of the pregnant guinea pig with IGFs promotes placental transport and nutrition partitioning near term. Am J Physiol Endocrinol Metab. 2006; 292, E668E676.Google Scholar
146.Audette, MC, Challis, JR, Jones, RL, Sibley, CP, Matthews, SG. Antenatal dexamethasone treatment in midgestation reduces system A-mediated transport in the late-gestation murine placenta. Endocrinology. 2011; 152, 35613570.Google Scholar
147.Desoye, G, Hartmann, M, Blaschitz, A, et al. Insulin receptors in syncytiotrophoblast and fetal endothelium of human placenta. Immunohistochemical evidence for developmental changes in distribution pattern. Histochemistry. 1994; 101, 277285.Google Scholar
148.Ebenbichler, CF, Kasser, S, Laimer, M, et al. Polar expression and phosphorylation of human leptin receptor isoforms in paired syncytial, microvillous and basal membranes from human term placenta. Placenta. 2002; 23, 516521.Google Scholar
149.Fang, J, Furesz, TC, Lurent, RS, Smith, CH, Fant, M. Spatial polarization of insulin-like growth factor receptors on the human syncytiotrophoblast. Pediatr Res. 1997; 41, 258265.Google Scholar
150.Jansson, T, Aye, ILMH, Goberdhan, DCI. The emerging role of mTORC1 signalling in placental nutrient-sensing. Placenta. 2012 June 9. [Epub ahead of print].Google Scholar
151.Yung, HW, Calabrese, S, Hynx, D, et al. Evidence of translation inhibition and endoplasmic reticulum stress in the etiology of human intrauterine growth restriction. Am J Pathol. 2008; 173, 311314.Google Scholar
152.Zoncu, R, Efeyan, A, Sabatini, DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol. 2011; 12, 2135.Google Scholar
153.Roos, S, Kanai, Y, Prasad, PD, Powell, TL, Jansson, T. Regulation of placental amino acid transporter activity by mammalian target of rapamycin. Am J Physiol Cell. 2009; 296, C142C150.Google Scholar
154.Roos, S, Jansson, N, Palmberg, I, et al. Mammalian target of rapamycin in the human placenta regulates leucine transport and is down-regulated in restricted foetal growth. J Physiol. 2007; 582, 449459.Google Scholar
155.Gaccioli, F, Jansson, T, Powell, TL. Activation of placental mammalian target of rapamycin signaling in obese women. Placenta. 2011; 32, A134 Abstract.Google Scholar
156.Arroyo, JA, Brown, LD, Galan, HL. Placental mammalian target of rapamycin and related signaling pathways in an ovine model of intrauterine growth restriction. Am J Obstet Gynecol. 2009; 201, 616e611616e617.Google Scholar
157.Coan, PM, Burton, GJ, Ferguson-Smith, AC. Imprinted genes in the placenta – a review. Placenta. 2005; 26(Suppl. A), S10S20.Google Scholar
158.Coan, PM, Fowden, AL, Constancia, M, et al. Disproportional effects of Igf2 knockout on placental morphology and diffusional exchange characteristics in the mouse. J Physiol. 2008; 586, 50235032.Google Scholar
159.Smerieri, A, Petraroli, M, Ziveri, MA, et al. Effects of cord serum insulin, IGF-II, IGFBP-2, IL-6 and cortisol concentrations on human birth weight and length: pilot study. PLoS One. 2011; 6, e29562.Google Scholar
160.Christou, H, Connors, JM, Ziotopoulou, M, et al. Cord blood leptin and insulin-like growth factor levels are independent predictors of fetal growth. J Clin Endocrinol Metab. 2001; 86, 935938.Google Scholar
161.Strid, H, Care, AD, Jansson, T, Powell, TL. PTHrp midmolecule stimulates Ca2+ ATPase in human syncytiotrophoblast basal membrane. J Endocrinol. 2002; 175, 517524.Google Scholar
162.Godfrey, KM, Matthews, N, Glazier, J, et al. Neutral amino acid uptake by microvillous plasma membrane of the human placenta is inversely related to fetal size at birth in normal pregnancy. J Clin Endocrinol Metab. 1998; 83, 33203326.Google Scholar