Placental adaptations in growth restriction

Nutrients

Volumn 7, Issue 1, 2015, Pages 360-389

  Zhang, Song ^a   Regnault, Timothy R H ^b   Barker, Paige L ^a   Botting, Kimberley J ^a   McMillen, Isabella C ^a   McMillan, Christine M ^a   Roberts, Claire T ^c   Morrison, Janna L ^a  

^a UNIVERSITY OF SOUTH AUSTRALIA   (Australia)

^b UNIVERSITY OF WESTERN ONTARIO   (Canada)

^c UNIVERSITY OF ADELAIDE   (Australia)

Author keywords

IUGR; Placental morphology; Substrate transport; Vascularity

Indexed keywords

11BETA HYDROXYSTEROID DEHYDROGENASE 2; AMINO ACID; AMINO ACID TRANSPORTER; FATTY ACID; FATTY ACID TRANSPORTER; GLUCOCORTICOID; GLUCOSE; GLUCOSE TRANSPORTER; OXYGEN; SOMATOMEDIN; SOMATOMEDIN RECEPTOR;

AMINO ACID TRANSPORT; APOPTOSIS; ARTERY LIGATION; AUTOPHAGY; EMBOLISM; FATTY ACID TRANSPORT; FETUS DEVELOPMENT; GLUCOSE TRANSPORT SYSTEM; HUMAN; HYPERTHERMIA; INTRAUTERINE GROWTH RETARDATION; NONHUMAN; OXYGENATION; PERINATAL MORTALITY; PLACENTA; PLACENTA CIRCULATION; PLACENTA DEVELOPMENT; PLACENTA INSUFFICIENCY; PLACENTAL TRANSFER; REVIEW; ADAPTATION; ANIMAL; ANIMAL MODEL; BIOLOGICAL MODEL; FEMALE; METABOLISM; PATHOPHYSIOLOGY; PREGNANCY; TRANSPORT AT THE CELLULAR LEVEL;

ANIMALIA;

ADAPTATION, PHYSIOLOGICAL; AMINO ACIDS; ANIMALS; BIOLOGICAL TRANSPORT; FATTY ACIDS; FEMALE; FETAL DEVELOPMENT; FETAL GROWTH RETARDATION; GLUCOSE; HUMANS; MODELS, ANIMAL; MODELS, BIOLOGICAL; PLACENTA; PREGNANCY;

EID: 84920991950     PISSN: None     EISSN: 20726643     Source Type: Journal    
DOI: 10.3390/nu7010360     Document Type: Review

References (184)

1. Li, Z.; Zeki, R.; Hilder, L.; Sullivan, E.A. Australia’s Mothers and Babies 2010, Ca. no. PER 57 ed.; AIHW National Perinatal Epidemiology and Statistics: Canberra, Australia, 2012.
2. Limesand, S.W.; Rozance, P.J.; Zerbe, G.O.; Hutton, J.C.; Hay, W.W., Jr. Attenuated insulin release and storage in fetal sheep pancreatic islets with intrauterine growth restriction. Endocrinology 2006, 147, 1488–1497.
3. Bamfo, J.E.; Odibo, A.O. Diagnosis and management of fetal growth restriction. J. Pregnancy 2011, 2011, doi:10.1155/2011/640715.
4. Barker, D.J. Developmental origins or chronic disease. Public Healh 2012, 126, 185–189.
5. Barker, D.J.; Gluckman, P.D.; Godfrey, K.M.; Harding, J.E.; Owens, J.A.; Robinson, J.S. Fetal nutrition and cardiovascular disease in adult life. Lancet 1993, 341, 938–941.
6. Li, C.C.Y.; Maloney, C.A.; Cropley, J.E.; Suter, C.M. Epigenetic programming by maternal nutritions: Shaping future generations. Epigenomics 2010, 2, 539–549.
7. Barker, D.J.; Gelow, J.; Thornburg, K.; Osmond, C.; Kajantie, E.; Eriksson, J.G. The early origins of chronic heart failure: Impaired placental growth and initiation of insulin resistance in childhood. Eur. J. Heart Fail. 2010, 12, 819–825.
8. Jansson, T.; Powell, T.L. Role of the placenta in fetal programming: Underlying mechanisms and potential interventional approaches. Clin. Sci. (Lond.) 2007, 113, 1–13.
9. Jones, H.N.; Powell, T.L.; Jansson, T. Regulation of placental nutrient transport-A review. Placenta 2007, 28, 763–774.
10. Marconi, A.M.; Paolini, C.L. Nutrient transport across the intrauterine growth-restricted placenta. Semin. Perinatol. 2008, 32, 178–181.
11. Gude, N.M.; Roberts, C.T.; Kalionis, B.; King, R.G. Growth and function of the normal human placenta. Thromb. Res. 2004, 114, 397–407.
12. Sibley, C.P.; Brownbill, P.; Dilworth, M.; Glazier, J.D. Review: Adaption in placental nutrient supply to meet fetal growth demand: Implications for programmings. Placenta 2010, 24, 70–74.
13. Lager, S.; Powell, T.L. Regulation of nutrient transport across the placenta. J. Pregnancy 2012, 2012, 1–14.
14. Barry, J.S.; Anthony, R.V. The pregnant sheep as a model for human pregnancy. Theriogenology 2008, 69, 55–67.
15. Fowden, A.L.; Ward, J.W.; Wooding, F.P.B.; Forhead, A.J.; Constancia, M. Programming placental nutrient transfer capacity. J. Physiol. 2006, 572, 5–15.
16. Ward, J.W.; Forhead, A.J.; Wooding, F.P.B.; Fowden, A.L. Functional significance and cortisol dependence of the gross morphology of ovine placentomes during late gestation. Biol. Reprod. 2006, 74, 137–145.
17. Ahokas, R.A.; McKinney, E.T. Development and Physiology of the Placenta and Membrane; The Global Library of Women ’s Medicine: London, UK, 2008.
18. Fowden, A.L.; Sferruzzi-Perri, A.N.; Coan, P.M.; Burton, G. Placental efficiency and adaptation: Endocrine regulation. J. Physiol. 2009, 587, 3459–3472.
19. Regnault, T.R.; Marconi, A.M.; Smith, C.H.; Glazier, J.D.; Novak, D.A.; Sibley, C.P.; Jansson, T. Placental amino acid transport systems and fetal growth restriction-A workshop report. Placenta 2005, 26, 76–80.
20. Roberts, C.T.; Sohlstrom, A.; Kind, K.L.; Grant, P.A.; Earl, R.A.; Robinson, J.S.; Khong, T.Y.; Owens, P.C.; Owens, J.A. Altered placental structure induced by maternal food restriction in guinea pigs: A role for circulating IGF-2 and IGFBP-2 in the mother? Placenta 2001, 22, 77–82.
21. Anthony, R.V.; Scheaffer, A.N.; Wright, C.D.; Regnault, T.R. Ruminant models of prenatal growth restriction. Reprod. Suppl. 2003, 61, 183–194.
22. Regnault, T.R.; de Vrijer, B.; Galan, H.L.; Wilkening, R.B.; Battaglia, F.C.; Meschia, G. Umbilical uptakes and transplacental concentration ratios of amino acids in severe fetal growth restriction. Pediatr. Res. 2013, 73, 602–611.
23. Morrison, J.L. Sheep models of intrauterine growth restriction: Fetal adaptations and consequences. Clin. Exp. Pharmacol. Physiol. 2008, 35, 730–743.
24. Gagnon, R.; Langridge, J.; Inchley, K.; Murotsuki, J.; Possmayer, F. Changes in surfactant-associated protein mRNA profile in growth-restricted fetal sheep. Am. J. Physiol. 1999, 276, 459–465.
25. Jones, C.T.; Roebuck, M.M.; Walker, D.W.; Lagercrantz, H.; Johnston, B.M. Cardiovascular, metabolic and endocrine effects of chemical sympathectomy and of adrenal demedullation in fetal sheep. J. Dev. Physiol. 1987, 9, 347–367.
26. Miller, S.L.; Chai, M.; Loose, J.; Castillo-Melendez, M.; Walker, D.W.; Jenkin, G.; Wallace, E.M. The effects of maternal betamethasone administration on the intrauterine growth-restricted fetus. Endocrinology 2007, 148, 1288–1295.
27. Mallard, E.C.; Rees, S.; Stringer, M.; Cock, M.L.; Harding, R. Effects of chronic placental insufficiency on brain development in fetal sheep. Pediatr. Res. 1998, 43, 262–270.
28. Robinson, J.S.; Hart, I.C.; Kingston, E.J.; Jones, C.T.; Thorburn, G.D. Studies on the growth of the fetal sheep. The effects of reduction of placental size on hormone concentration in fetal plasma. J. Dev. Physiol. 1980, 2, 239–248.
29. Dobbing, J.; Sands, J. Comparative aspects of the brain growth spurt. Early Hum. Dev. 1979, 3, 79–83.
30. Regnault, T.R.H.; de Vrijer, B.; Galan, H.L.; Wilkening, R.B.; Battaglia, F.C.; Meschia, G. Development and mechanisms of fetal hypoxia in severe fetal growth restriction. Placenta 2007, 28, 714–723.
31. Wilson, M.E. Role of placental function in mediating conceptus growth and survival. J. Anim. Sci. 2002, 80, 195–201.
32. Vonnahme, K.A.; Arndt, W.J.; Johnson, M.L.; Borowicz, P.P.; Reynolds, L.P. Effect of morphology on placentome size, vascularity and vasoreactivity in late pregnant sheep. Biol. Reprod. 2008, 79, 976–982.
33. Ehrhardt, R.A.; Bell, A.W. Growth and metabolism of the ovine placenta during mid-gestation. Placenta 1995, 16, 727–741.
34. Vatnick, I.; Schoknecht, P.A.; Darrigrand, R.; Bell, A.W. Growth and metabolism of the placenta after unilateral fetectomy in twin pregnant ewes. J. Dev. Physiol. 1991, 15, 351–356.
35. Robinson, J.S.; Hartwich, K.M.; Walker, S.K.; Erwich, J.J.; Owens, J.A. Early influences on embryonic and placental growth. Acta Paediatr. Suppl. 1997, 423, 159–164.
36. Alexander, G. Studies on the placenta of the sheep (Ovis aries L.). Effect of surgical reduction in the number of caruncles. J. Reprod. Fertil. 1964, 30, 307–322.
37. Wilson, M.E.; Ford, S.P. Comparative aspects of placental efficiency. Reprod. Suppl. 2001, 58, 223–232.
38. Barker, D.J.P.; Thornburg, K.L. Placental programming of chronic diseases, cancer and lifespan: A review. Placenta 2013, 34, 841–845.
39. Barker, D.J.; Bull, A.R.; Osmond, C.; Simmonds, S.J. Fetal and placental size and risk of hypertension in adult life. BMJ 1990, 301, 259–262.
40. Sibai, B.M.; Frangieh, A. Maternal adaptation to pregnancy. Curr. Opin. Obstet. Gynecol. 1995, 7, 420–426.
41. Carter, A.M. Factors affecting gas transfer across the placenta and the oxygen supply to the fetus. J. Dev. Physiol. 1989, 12, 305–322.
42. Bell, A.W.; Kennaugh, J.M.; Battaglia, F.C.; Makowski, E.L.; Meschia, G. Metabolic and circulatory studies of fetal lamb at midgestation. Am. J. Physiol. 1986, 250, 538–544.
43. Bonds, D.R.; Crosby, L.O.; Cheek, T.G.; Hagerdal, M.; Gutsche, B.B.; Gabbe, S.G. Estimation of human fetal-placental unit metabolic rate by application of the bohr principle. J. Dev. Physiol. 1986, 8, 49–54.
44. Campbell, A.G.; Dawes, G.S.; Fishman, A.P.; Hyman, A.I.; James, G.B. The oxygen consumption of the placenta and foetal membranes in the sheep. J. Physiol. 1966, 182, 439–464.
45. Coan, P.M.; Ferguson-Smith, A.C.; Burton, G. Developmental dynamics of the definitive mouse placenta assessed by stereology. Biol. Reprod. 2004, 70, 1806–1813.
46. Reynolds, L.P.; Borawicz, P.P.; Vonnahme, K.A.; Johnson, M.L.; Grazul-Bilska, A.T.; Wallace, J.M.; Caton, J.S.; Redmer, D.A. Animal models of placental angiogenesis. Placenta 2005, 26, 689–708.
47. Demir, R.; Seval, Y.; Huppertz, B. Vasculogenesis and angiogenesis in the early human placenta. Acta Histochem. 2007, 109, 257–265.
48. Charnock-Jones, D.S.; Kaufmann, P.; Mayhew, T.M. Aspects of human fetoplacental vasculogenesis and angiogenesis. I. Molecular regulation. Placenta 2004, 25, 103–113.
49. Ahmed, A.; Perkins, J. Angiogenesis and intrauterine growth restriction. Baillieres Best Pract. Res. Clin. Obstet. Gynaecol. 2000, 14, 981–998.
50. Maisonpierre, P.C.; Suri, C.; Jones, P.F.; Bartunkova, S.; Wiegand, S.J.; Radziejewski, C.; Compton, D.; McClain, J.; Aldrich, T.H.; Papadopoulos, N.; et al. Angiopoietin-2, a natural antagonist for tie2 that disrupts in vivo angiogenesis. Science 1997, 277, 55–60.
51. Plaisier, M.; Rodrigues, S.; Willems, F.; Koolwijk, P.; van Hinsbergh, V.W.; Helmerhorst, F.M. Different degrees of vascularization and their relationship to the expression of vascular endothelial growth factor, placental growth factor, angiopoietins, and their receptors in first-trimester decidual tissues. Fertil. Steril. 2007, 88, 176–187.
52. Cross, J.C.; Hemberger, M.; Lu, Y.; Nozaki, T.; Whiteley, K.; Masutani, M.; Adamson, S.L. Trophoblast functions, angiogenesis and remodeling of the maternal vasculature in the placenta. Mol. Cell. Endocrinol 2002, 187, 207–212.
53. Regnault, T.R.; de Vrijer, B.; Galan, H.L.; Davidsen, M.L.; Trembler, K.A.; Battaglia, F.C.; Wilkening, R.B.; Anthony, R.V. The relationship between transplacental O2 diffusion and placental expression of PLGF, VEGF and their receptors in a placental insufficiency model of fetal growth restriction. J. Physiol. 2003, 550, 641–656.
54. Hagen, A.S.; Orbus, R.J.; Wilkening, R.B.; Regnault, T.R.; Anthony, R.V. Placental expression of angiopoietin-1, angiopoietin-2 and tie-2 during placental development in an ovine model of placental insufficiency-fetal growth restriction. Pediatr. Res. 2005, 58, 1228–1232.
55. Fowden, A.L.; Forhead, A.J.; Coan, P.M.; Burton, G. The placenta and intrauterine programming. J. Neuroendocrinol. 2008, 20, 439–450.
56. Sferruzzi-Perri, A.N.; Owens, J.A.; Pringle, K.G.; Roberts, C.T. The neglected role of insulin-like growth factors in the maternal circulation regulating fetal growth. J. Physiol. 2011, 589, 7–20.
57. Roos, S.; Lagerlöf, O.; Wennergren, M.; Powell, T.L.; Jansson, T. Regulation of amino acid transporters by glucose and growth factors in cultured primary human trophoblast cells is mediated by mtor signalling. Am. J. Physiol. Cell Physiol. 2009, 297, 723–731.
58. Harding, J.E.; Liu, L.; Evans, P.C.; Gluckman, P.D. Insulin-like growth factor 1 alters feto-placental protein and carbohydrate metabolism in fetal sheep. Endocrinology. 1994, 134, 1509–1514.
59. Constancia, M.; Angiolini, E.; Sandovic, I.; Smith, P.; Smith, R.; Kelsey, G.; Dean, W.; Ferguson-Smith, A.C.; Sibley, C.P.; Reik, W.; et al. Adaption of nutrient supply to fetal demand in the mouse involves interaction between the Igf2 gene and placental transporter proteins. Proc. Natl. Acad. Sci. USA 2005, 102, 19219–19224.
60. Sibley, C.P.; Coan, P.M.; Ferguson-Smith, A.C.; Dean, W.; Hughes, J.; Smith, P.; Reik, W.; Burton, G.J.; Fowden, A.L.; Constancia, M. Placental-specific insulin-like growth factor 2 (Igf2) regulates the diffusional exchange characteristics of the mouse placenta. Proc. Natl. Acad. Sci. USA 2004, 101, 8204–8208.
61. Constancia, M.; Hemberger, M.; Hughes, J.; Dean, W.; Ferguson-Smith, A.; Fundele, R.; Stewart, F.; Kelsey, G.; Fowden, A.; Sibley, C.; et al. Placental-specific IGF-2 is a major modulator of placental and fetal growth. Nature 2002, 417, 945–948.
62. Huppertz, B.; Kadyrov, M.; Kingdom, J.C. Apoptosis and its role in the trophoblast. Am. J. Obstet. Gynecol. 2006, 195, 29–39.
63. Klionsky, D.J.; Emr, S.D. Autophagy as a regulated pathway of cellular degradation. Science 2000, 290, 1717–1721.
64. Signorelli, P.; Avagliano, L.; Virgili, E.; Gagliostro, V.; Doi, P.; Braidotti, P.; Bulfamante, G.P.; Ghidoni, R.; Marconi, A.M. Autophagy in term normal human placentas. Placenta 2011, 32, 482–485.
65. Hung, T.H.; Hsieh, T.T.; Chen, S.F.; Li, M.J.; Yeh, Y.L. Autophagy in the human placenta throughout gestation. PLoS One 2013, 8, doi:10.1371/journal.pone.0083475.
66. Klionsky, D.J.; Abdalla, F.C.; Abeliovich, H.; Abraham, R.T.; Acevedo-Arozena, A.; Adeli, K.; Agholme, L.; Agnello, M.; Agostinis, P.; Aguirre-Ghiso, J.A.; et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 2012, 8, 445–544.
67. Crighton, D.; Wilkinson, S.; Ryan, K.M. Dram links autophagy to p53 and programmed cell death. Autophagy 2007, 3, 72–74.
68. Michael, A.E.; Thurston, L.M.; Rae, M.T. Glucocorticoid metabolism and reproduction: A tale of two enzymes. Reproduction 2003, 126, 425–441.
69. Korgun, E.T.; Ozmen, A.; Unek, G.; Mendilcioglu, I. The Effects of Glucocorticoids on Fetal and Placental Development; InTech: Rijeka, Croatia, 2012.
70. Alfaidy, N.; Li, W.; MacIntosh, T.; Yang, K.; Challis, J. Late gestation increase in 11beta-hydroxysteroid dehydrogenase 1 expression in human fetal membranes: A novel intrauterine source of cortisol. J. Clin. Endocrinol. Metab. 2003, 88, 5033–5038.
71. Shams, M.; Kilby, M.D.; Somerset, D.A.; Howie, A.J.; Gupta, A.; Wood, P.J.; Afnan, M.; Stewart, P.M. 11beta-hydroxysteroid dehydrogenase type 2 in human pregnancy and reduced expression in intrauterine growth restriction. Hum. Reprod. 1998, 13, 799–804.
72. Whorwood, C.B.; Firth, K.M.; Budge, H.; Symonds, M.E. Maternal undernutrition during early to midgestation programs tissue-specific alterations in the expression of the glucocorticoid receptor, 11beta-hydroxysteroid dehydrogenase isoforms, and type 1 angiotensin 2 receptor in neonatal sheep. Endocrinology 2001, 142, 2854–2864.
73. Sibley, C.P.; Turner, M.A.; Cetin, I.; Ayuk, P.; Boyd, R.; D’Souza, S.W.; Glazier, J.D.; Greenwood, S.L.; Jansson, T.; Powell, T.L. Placental phenotypes of intrauterine growth. Pediatr. Res. 2005, 58, 827–832.
74. Brown, K.; Heller, D.S.; Zamudio, S.; Illsley, N.P. Glucose transporter 3 (GLUT3) protein expression in human placenta across gestation. Placenta 2011, 32, 1041–1049.
75. Magnusson, A.L.; Powell, T.L.; Wennergren, M.; Jansson, T. Glucose metabolism in the the human preterm and term placenta of IUGR fetuses. Placenta 2004, 25, 337–346.
76. DiGiacomo, J.E.; Hay, W.W., Jr. Placental-fetal glucose exchange and placental glucose consumption in pregnant sheep. Am. J. Physiol. 1990, 258, 360–367.
77. Hay, W.W., Jr. Placental-fetal glucose exchange and fetal glucose metabolism. Trans. Am. Clin. Climatol. Assoc. 2006, 117, 321–340.
78. Novakovic, B.; Gordon, L.; Robinson, W.P.; Desoye, G.; Saffery, R. Glucose as a fetal nutrients: Dynamic regulation of several glucose transporter genes by DNA methylation in the human placenta across gestation. J. Nutr. Biochem. 2013, 24, 282–288.
79. Dandrea, J.; Wilson, V.; Gopalakrishnan, G.; Heasman, L.; Budge, H.; Stephenson, T.; Symonds, M.E. Maternal nutritional manipulation of placental growth and glucose transporter 1 (GLUT-1) abundance in sheep. Reproduction 2001, 122, 793–800.
80. Larqué, E.; Ruiz-Palacios, M.R.; Koletzko, B. Placental regulation of fetal nutrient supply. Curr. Opin. Clin. Nutr. Metab. Care 2013, 16, 292–297.
81. Wooding, F.B.; Fowden, A.L.; Bell, A.W.; Ehrhardt, R.A.; Limesand, S.W.; Hay, W.W., Jr. Localisation of glucose transport in the ruminant placenta: Implications for sequential use of transporter isoforms. Placenta 2005, 26, 626–640.
82. Wolf, H.J.; Desoye, G. Immunohistochemical localization of glucose transporters and insulin receptors in human fetal membranes at term. Histochemistry 1993, 100, 379–385.
83. Xing, A.Y.; Challier, J.C.; Lepercq, J.; Cauzac, M.; Charron, M.J.; Girard, J.; Hauguel-de Mouzon, S. Unexpected expression of glucose transporter 4 in villous stromal cells of human placenta. J. Clin. Endocrinol. Metab. 1998, 83, 4097–4101.
84. Limesand, S.W.; Regnault, T.R.; Hay, W.W., Jr. Characterization of glucose transporter 8 (GLUT8) in the ovine placenta of normal and growth restricted fetuses. Placenta 2004, 25, 70–77.
85. Carayannopoulos, M.O.; Chi, M.M.; Cui, Y.; Pingsterhaus, J.M.; McKnight, R.A.; Mueckler, M.; Devaskar, S.U.; Moley, K.H. GLUT8 is a glucose transporter responsible for insulin-stimulated glucose uptake in the blastocyst. Proc. Natl. Acad. Sci. USA 2000, 97, 7313–7318.
86. Regnault, T.R.H.; Friedman, J.E.; Wilkening, R.B.; Anthony, R.V.; Hay, W.W., Jr. Fetoplacental transport and utilization of amino acids in IUGR. A review. Placenta 2005, 26, 52–62.
87. Grillo, M.A.; Lanza, A.; Colombatto, S. Transport of amino acids through the placenta and their role. Amino Acids 2008, 34, 517–523.
88. Desforges, M.; Sibley, C.P. Placental nutrient supply and fetal growth. Int. J. Dev. Biol. 2010, 54, 377–390.
89. Desforges, M.; Lacey, H.A.; Glazier, J.D.; Greenwood, S.L.; Mynett, K.J.; Speake, P.F.; Sibley, C.P. Snat4 isoform of system A amino acid transporter is expressed in human placenta. Am. J. Physiol. Cell Physiol. 2006, 290, 305–312.
90. Regnault, T.R.H.; de Vrijer, B.; Battaglia, F.C. Transport and metabolism of amino acids in placenta. Endocrine 2002, 19, 23–41.
91. Desforges, M.; Greenwood, S.L.; Glazier, J.D.; Westwood, M.; Sibley, C.P. The contribution of snat1 to system A amino acid transporter activity in human placental trophoblast. Biochem. Biophys. Res. Commun. 2010, 398, 130–134.
92. Verrey, F, System l.: Heteromeric exchangers of large, neutral amino acids involved in directional transport. Pflugers Arch. 2003, 445, 529–533.
93. Okamoto, Y.; Sakata, M.; Ogura, K.; Yamamoto, T.; Yamaguchi, M.; Tasaka, K.; Kurachi, H.; Tsurudome, M.; Murata, Y. Expression and regulation of 4f2hc and hlat1 in human trophoblasts. Am. J. Physiol. 2002, 282, 196–204.
94. Gaccioli, F.; Roos, S.; Powell, T.L.; Jansson, T. Isoforms of the system L-amino acid transporter are differentially polarised to the syncytiotrophoblast plasma membrane in human placenta. Reprod. Sci. 2011, 18, 200.
95. Lewis, R.M.; Glazier, J.D.; Greenwood, S.L.; Bennett, E.J.; Godfrey, K.M.; Jackson, A.A.; Sibley, C.P.; Cameron, I.T.; Hanson, M.A. L-serine uptake by human placental microvillous membrane vesicles. Placenta 2007, 28, 445–452.
96. Kudo, Y.; Boyd, C.A.R. Characterisation of L-tryptophan transporters in human placenta: A comparison of brush border and basal membrane vesicles. J. Physiol. 2001, 531, 405–416.
97. Bodoy, S.; Martin, L.; Zorzano, A.; Palacin, M.; Estevez, R.; Bertran, J. Identification of lat4, a novel amino acid transporter with system l activity. J. Biol. Chem. 2005, 280, 12002–12011.
98. Babu, E.; Kanai, Y.; Chairoungdua, A.; Kim, D.K.; Iribe, Y.; Tangtrongsup, S.; Jutabha, P.; Li, Y.; Ahmed, N.; Sakamoto, S.; et al. Identification of a novel system l amino acid transporter structurally distinct from heterodimeric amino acid transporters. J. Biol. Chem. 2003, 278, 43838–43845.
99. Cleal, J.K.; Glazier, J.D.; Ntani, G.; Crozier, S.R.; Day, P.E.; Harvey, N.C.; Robinson, S.M.; Cooper, C.; Godfrey, K.M.; Hanson, M.A.; et al. Facilitated transporters mediate net efflux of amino acids to the fetus across the basal membrane of the placental syncytiotrophoblast. J. Physiol. 2011, 589, 987–997.
100. Cleal, J.K.; Brownbill, P.; Godfrey, K.M.; Jackson, J.M.; Jackson, A.A.; Sibley, C.P.; Hanson, M.A.; Lewis, R.M. Modification of fetal plasma amino acid composition by placental amino acid exchangers in vitro. J. Physiol. 2007, 582, 871–882.
101. Ayuk, P.T.; Sibley, C.P.; Donnai, P.; D’Souza, S.; Glazier, J.D. Development and polarization of cationic amino acid transporters and regulators in the human placenta. Am. J. Physiol. Cell Physiol. 2000, 278, 1162–1171.
102. Kamath, S.G.; Furesz, T.C.; Way, B.A.; Smith, C.H. Identification of three cationic amino acid transporters in placental trophoblast: Cloning, expression, and characterization of hcat-1. J. Membr. Biol. 1999, 171, 55–62.
103. Arriza, J.L.; Fairman, W.A.; Wadiche, J.I.; Murdoch, G.H.; Kavanaugh, M.P.; Amara, S.G. Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex. J. Neurosci. 1994, 14, 5559–5569.
104. Fairman, W.A.; Vandenberg, R.J.; Arriza, J.L.; Kavanaugh, M.P.; Amara, S.G. An excitatory amino-acid transporter with properties of a ligand-gated chloride channel. Nature 1995, 375, 599–603.
105. Matthews, J.C.; Beveridge, M.J.; Malandro, M.S.; Rothstein, J.D.; Campbell-Thompson, M.; Verlander, J.W.; Kilberg, M.S.; Novak, D.A. Activity and protein localization of multiple glutamate transporters in gestation day 14 vs. Day 20 rat placenta. Am. J. Physiol. 1998, 274, 603–614.
106. Jansson, T. Amino acid transporters in the human placenta. Pediatr. Res. 2001, 49, 141–147.
107. Haggarty, P. Fatty acid supply to the human fetus. Annu. Rev. Nutr. 2010, 30, 237–255.
108. Kazantzis, M.; Stahl, A. Fatty acid transport proteins, implications in physiology and disease. Biochim. Biophys. Acta 2012, 1821, 852–857.
109. Schaiff, W.T.; Bildirici, I.; Cheong, M.; Chern, P.L.; Nelson, D.M.; Sadovsky, Y. Peroxisome proliferator-activated receptor-γ and retinoid X receptor signaling regulate fatty acid uptake by primary human placental trophoblasts. J. Clin. Endocrinol. Metab. 2005, 90, 4267–4275.
110. Campbell, F.M.; Bush, P.G.; Veerkamp, J.H.; Dutta-Roy, A.K. Detection and cellular localization of plasma membrane-associated and cytoplasmic fatty acid-binding proteins in human placenta. Placenta 1998, 19, 409–415.
111. Biron-Shental, T.; Schaiff, W.T.; Ratajczak, C.K.; Bildirici, I.; Nelson, D.M.; Sadovsky, Y. Hypoxia regulates the expression of fatty acid-binding proteins in primary term human trophoblasts. Am. J. Obstet. Gynecol. 2007, 197, 1–6.
112. McMillen, I.C.; Robinson, J.S. Developmental origins of the metabolic syndrome: Prediction, plasticity, and programming. Physiol. Rev. 2005, 85, 571–633.
113. Barker, D.J. Fetal programming of coronary heart disease. Trends Endocrinol. Metab. 2002, 13, 364–368.
114. Barker, D.J.; Osmond, C.; Forsen, T.J.; Kajantie, E.; Eriksson, J.G. Trajectories of growth among children who have coronary events as adults. N. Engl. J. Med. 2005, 353, 1802–1809.
115. Moore, V.M.; Miller, A.G.; Boulton, T.J.C.; Cockington, R.A.; Craig, I.H.; Magarey, A.M.; Robinson, J.S. Placental weight, birth measurements and blood pressure at age 8 years. Arch. Dis. Child. 1996, 74, 538–541.
116. McMillen, I.C.; Adams, M.B.; Ross, J.T.; Coulter, C.L.; Simonetta, G.; Owens, J.A.; Robinson, J.S.; Edwards, L.J. Fetal growth restriction: Adaptations and consequences. Reproduction 2001, 122, 195–204.
117. Morrison, J.L.; Duffield, J.A.; Muhulhausler, B.S.; Gentili, S.; McMillen, I.C. Fetal growth restriction, catch-up growth and the early origins of insulin resistance and visceral obesity. Pediatr. Nephrol. 2009, 25, 669–677.
118. Emmanouilides, G.C.; Townsend, D.E.; Bauer, R.A. Effects of single umbilical artery ligation in the lamb fetus. Pediatrics 1968, 42, 919–927.
119. Oh, W.; Omori, K.; Erenberg, A.; Emmanouilides, G.C. Umbilical blood flow and glucose uptake in lamb fetus following single umbilical artery ligation. Biol. Neonate 1975, 26, 291–299.
120. Cheung, C.Y.; Bogic, L.; Gagnon, R.; Harding, R.; Brace, R.A. Morphologic alterations in ovine placenta and fetal liver following induced severe placental insufficiency. J. Soc. Gynecol. Investig. 2004, 11, 521–528.
121. Sutherland, A.E.; Crossley, K.J.; Allison, B.J.; Jenkin, G.; Wallace, E.M.; Miller, S.L. The effects of intrauterine growth restriction and antenatal glucocorticoids on ovine fetal lung development. Pediatr. Res. 2012, 76, 689–696.
122. Early, R.J.; McBride, B.W.; Vatnick, I.; Bell, A.W. Chronic heat stress and prenatal development in sheep: 2. Placental cellularity and metabolism. J. Anim. Sci. 1991, 69, 3610–3616.
123. Regnault, T.R.; Orbus, R.J.; de Vrijer, B.; Davidsen, M.L.; Galan, H.L.; Wilkening, R.B.; Anthony, R.V. Placental expression of VEGF, PLGF and their receptors in a model of placental insufficiency-intrauterine growth restriction (PI-IUGR). Placenta 2002, 23, 132–144.
124. Clapp, J.F; Szeto, H.H.; Larrow, R.; Hewitt, J.; Mann, L.I. Umbilical blood flow response to embolization of the uterine circulation. Am. J. Obstet. Gynecol. 1980, 138, 60–67.
125. Gagnon, R.; Johnston, L.; Murotsuki, J. Fetal placental embolization in the late-gestation ovine fetus: Alterations in umbilical blood FLW and fetal heart rate patterns. Am. J. Obstet. Gynecol. 1996, 175, 63–72.
126. Louey, S.; Cock, M.L.; Stevenson, K.M.; Harding, R. Placental insufficiency and fetal growth restriction lead to postnatal hypotension and alterd postnatal growth in sheep. Pediatr. Res. 2000, 48, 808–814.
127. Owens, J.A.; Kind, K.L.; Carbone, F.; Robinson, J.S.; Owens, P.C. Circulating insulin-like growth factors-I and -2 and substrates in fetal sheep following restriction of placental growth. J. Endocrinol. 1994, 140, 5–13.
128. Danielson, L.; IMcMillen, I.C.; Dyer, J.L.; Morrison, J.L. Restriction of placental growth results in greater hypotensive response to α-adrenergic blockade in sheep during late gestation. J. Physiol. 2005, 563, 611–620.
129. Soo, P.S.; Hiscock, J.; Botting, K.J.; Roberts, C.T.; Davey, A.K.; Morrison, J.L. Maternal undernutrition reduces P-glycoprotein in guinea pigs placenta and developing brain in late gestation. Reprod. Toxicol. 2012, 33, 374–381.
130. Robinson, J.S.; Kingston, E.J.; Jones, C.T.; Thornburn, G.D. Studies on experimental growth retardation in sheep. The effect of removal of endometrial caruncles on fetal size and metabolism. J. Dev. Physiol. 1979, 1, 379–398.
131. Chen, C.P.; Bajoria, R.; Aplin, J.D. Decreased vascularization and cell proliferation in placentas of intrauterine growth-restricted fetuses with abnormal umbilical artery flow velocity waveforms. Am. J. Obstet. Gynecol. 2002, 187, 764–769.
132. Mayhew, T.M.; Ohadike, C.; Baker, P.N.; Crocker, I.P.; Mitchell, C.; Ong, S.S. Stereological investigation of placental morphology in pregnancies complicated by pre-eclampsia with and without intrauterine growth restriction. Placenta 2003, 24, 219–226.
133. Krebs, C.; Macara, L.M.; Leiser, R.; Bowman, A.W.; Greer, I.A.; Kingdom, J.C. Intrauterine growth restriction with absent end-diastolic flow velocity in the umbilical artery is associated with maldevelopment of the placental terminal villous tree. Am. J. Obstet. Gynecol. 1996, 175, 1534–1542.
134. Roberts, C.T.; Owens, P.C.; Owens, J.A. Maternal food restriction reduces the exchange surface area and increases the barrier thickness of the placenta in the guinea pig. Placenta 2001, 22, 177–185.
135. Bacon, B.J.; Gilbert, R.D.; Kaufmann, P.; Smith, A.D.; Trevino, F.T.; Longo, L.D. Placental anatomy and diffusing capacity in guinea pigs following long-term maternal hypoxia. Placenta 1984, 5, 475–487.
136. Reshetnikova, O.S.; Burton, G.J.; Milovanov, A.P. Effects of hypobaric hypoxia on the fetoplacental unit: The morphometric diffusing capacity of the villous membrane at high altitude. Am. J. Obstet. Gynecol. 1994, 171, 1560–1565.
137. Parraguez, V.H.; Atlagich, M.; Diaz, R.; Cepeda, R.; Gonzalez, C.; de los Reyes, M.; Bruzzone, M.E.; Behn, C.; Raggi, L.A. Ovine placenta at high altitudes: Comparison of animals with different times of adaptation to hypoxic environment. Anim. Reprod. Sci. 2006, 95, 151–157.
138. Penninga, L.; Longo, L.D. Ovine placentome morphology: Effect of high altitude, long-term hypoxia. Placenta 1998, 19, 187–193.
139. Steyn, C.; Hawkins, P.; Saito, T.; Noakes, D.E.; Kingdom, J.C.P.; Hanson, M.A. Undernutrition during the first half of gestation increases the predominance of fetal tissue in late-gestation ovine placentomes. Eur. J. Obstet. Gynecol. Reprod. Biol. 2001, 98, 165–170.
140. Gardner, D.S.; Ward, J.W.; Giussani, D.A.; Fowden, A.L. The effect of a reversible period of adverse intrauterine conditions during late gestation on fetal and placental weight and placentome distribution in sheep. Placenta 2002, 23, 459–466.
141. Semenza, G.L. Hif-1: Mediator of physiological and pathophysiological responses to hypoxia. J. Appl. Physiol. 2000, 88, 1474–1480.
142. Caniggia, I.; Winter, J.L. Adriana and Luisa Castellucci award lecture 2001. Hypoxia inducible factor-1: Oxygen regulation of trophoblast differentiation in normal and pre-eclamptic pregnancies-A review. Placenta 2002, 23, 47–57.
143. Pringle, K.G.; Kind, K.L.; Thompson, J.G.; Roberts, C.T. Complex interactions between hypoxia inducible factors, insulin-like growth factor-2 and oxygen in early murine trophoblasts. Placenta 2007, 28, 1147–1157.
144. Wheeler, T.; Elcock, C.L.; Anthony, F.W. Angiogenesis and the placental environment. Placenta 1995, 16, 289–296.
145. Zhang, E.G.; Smith, S.K.; Baker, P.N.; Charnock-Jones, D.S. The regulation and localization of angiopoietin-1, -2, and their receptor tie2 in normal and pathologic human placentae. Mol. Med. 2001, 7, 624–635.
146. Toal, M.; Chan, C.; Fallah, S.; Alkazalen, F.; Chaddha, V.; Winderm, R.C.; Kingdom, J.C. Usefulness of a placental profile in high-risk pregnancies. Am. J. Obstet. Gynecol. 2007, 196, 363–371.
147. Pijnenborg, R.; Vercruysse, L.; Hanssens, M. The uterine spiral arteries in human pregnancy: Facts and controversies. Placenta 2006, 27, 939–958.
148. Lyall, F.; Young, A.; Boswell, F.; Kingdom, J.C.; Greer, I.A. Placental expression of vascular endothelial growth factor in placentae from pregnancies complicated by pre-eclampsia and intrauterine growth restriction does not support placental hypoxia at delivery. Placenta 1997, 18, 269–276.
149. Barut, F.; Barut, A.; Gun, B.D.; Kandemir, N.O.; Harma, M.I.; Harma, M.; Aktunc, E.; Ozdamar, S.O. Intrauterine growth restriction and placental angiogenesis. Diagn. Pathol. 2010, 5, doi:10.1186/ 1746-1596-5-24.
150. Akram, S.K.; Sahlin, L.; Ostlund, E.; Hagenas, L.; Fried, G.; Soder, O. Placental IGFI, estrogen receptor, and progesterone receptor expression, and maternal anthropometry in growth-restricted pregnancies in the swedish population. Horm. Res. Paediatr. 2011, 75, 131–137.
151. Koutsaki, M.; Sifakis, S.; Zaravinos, A.; Koutroulakis, D.; Koukoura, O.; Spandidos, D.A. Decreased placental expression of hPGH, IGF-I and IGFBP-1 in pregnancies complicated by fetal growth restriction. Growth Horm. IGF Res. 2011, 21, 31–36.
152. De Vrijer, B.; Davidsen, M.L.; Wilkening, R.B.; Anthony, R.V.; Regnault, T.R. Altered placental and fetal expression of IGFS and IGF-binding proteins associated with intrauterine growth restriction in fetal sheep during early and mid-pregnancy. Pediatr. Res. 2006, 60, 507–512.
153. Cuffe, J.S.; Walton, S.L.; Singh, R.R.; Spiers, J.G.; Bielefeldt-Ohmann, H.; Wilkinson, L.; Little, M.H.; Moritz, K.M. Mid- to late term hypoxia in the mouse alters placental morphology, glucocorticoid regulatory pathways and nutrient transporters in a sex-specific manner. J. Physiol. 2014, 592, 3127–3141.
154. Erel, C.T.; Dane, B.; Calay, Z.; Kaleli, S.; Aydinli, K. Apoptosis in the placenta of pregnancies complicated with iugr. Int. J. Gynaecol. Obstet. 2001, 73, 229–235.
155. Smith, S.C.; Baker, P.N.; Symonds, E.M. Increased placental apoptosis in intrauterine growth restriction. Am. J. Obstet. Gynecol. 1997, 177, 1395–1401.
156. Levy, R.; Smith, S.D.; Chandler, K.; Sadovsky, Y.; Nelson, D.M. Apoptosis in human cultured trophoblasts is enhanced by hypoxia and diminished by epidermal growth factor. Am. J. Physiol. Cell Physiol. 2000, 278, 982–988.
157. Hung, T.H.; Chen, S.F.; Liou, J.D.; Hsu, J.J.; Li, M.J.; Yeh, Y.L.; Hsieh, T.T. Bax, Bak and mitochondrial oxidants are involved in hypoxia-reoxygenation-induced apoptosis in human placenta. Placenta 2008, 29, 565–583.
158. Levy, R.; Smith, S.D.; Yusuf, K.; Huettner, P.C.; Kraus, F.T.; Sadovsky, Y.; Nelson, D.M. Trophoblast apoptosis from pregnancies complicated by fetal growth restriction is associated with enhanced p53 expression. Am. J. Obstet. Gynecol. 2002, 186, 1056–1061.
159. Endo, H.; Okamoto, A.; Yamada, K.; Nikaido, T.; Tanaka, T. Frequent apoptosis in placental villi from pregnancies complicated with intrauterine growth restriction and without maternal symptoms. Int. J. Mol. Med. 2005, 16, 79–84.
160. Heazell, A.E.; Sharp, A.N.; Baker, P.N.; Crocker, I.P. Intra-uterine growth restriction is associated with increased apoptosis and altered expression of proteins in the p53 pathway in villous trophoblast. Apoptosis 2011, 16, 135–144.
161. Hung, T.H.; Chen, S.F.; Lo, L.M.; Li, M.J.; Yeh, Y.L.; Hsieh, T.T. Increased autophagy in placentas of intrauterine growth-restricted pregnancies. PLoS One 2012, 7, doi:10.1371/journal. pone.0040957.
162. Chen, B.; Longtine, M.S.; Nelson, D.M. Hypoxia induces autophagy in primary human trophoblasts. Endocrinology 2012, 153, 4946–4954.
163. Jaquiery, A.L.; Oliver, M.H.; Bloomfield, F.H.; Connor, K.L.; Challis, J.R.; Harding, J.E. Fetal exposure to excess glucocorticoid is unlikely to explain the effects of periconceptional undernutrition in sheep. J. Physiol. 2006, 572, 109–118.
164. Mericq, V.; Medina, P.; Kakarieka, E.; Marquez, L.; Johnson, M.C.; Iniguez, G. Differences in expression and activity of 11beta-hydroxysteroid dehydrogenase type 1 and 2 in human placentas of term pregnancies according to birth weight and gender. Eur. J. Endocrinol. 2009, 161, 419–425.
165. Zamudio, S.; Torricos, T.; Fik, E.; Oyala, M.; Echalar, L.; Pullockaran, J.; Tutino, E.; Martin, B.; Belliappa, S.; Balanza, E.; et al. Hypoglycemia and the origin of hypoxia-induced reduction in human fetal growth. PLoS One 2010, 5, doi:10.1371/journal.pone.0008551.
166. Owens, J.A.; Falconer, J.; Robinson, J.S. Restriction of placental size in sheep enhances efficiency of placental transfer of antipyrine, 3-o-methyl-d-glucose but not of urea. J. Dev. Physiol. 1987, 9, 457–464.
167. Owens, J.A.; Falconer, J.; Robinson, J.S. Effect of restriction of placental growth on fetal and utero-placental metabolism. J. Dev. Physiol. 1987, 9, 225–238.
168. Baumann, M.U.; Zamudio, S.; Illsley, N.P. Hypoxic upregulation of glucose transporters in BeWo choriocarcinoma cells is mediated by hypoxia-inducible factor-1. Am. J. Physiol. Cell Physiol. 2007, 293, 477–485.
169. Janzen, C.; Lei, M.Y.; Cho, J.; Sullivan, P.; Shin, B.C.; Devaskar, S.U. Placental glucose transporter 3 (GLUT3) is up-regulated in human pregnancies complicated by late-onset intrauterine growth restriction. Placenta 2013, 34, 1072–1078.
170. Dubova, E.A.; Pavlov, K.A.; Kulikova, G.V.; Shchegolev, A.I.; Sukhikh, G.T. Glucose transporters expression in the placental terminal villi of preeclampsia and intrauterine growth retardation complicated pregnancies. Health 2013, 5, 100–104.
171. Zamudio, S.; Baumann, M.U.; Illsley, N.P. Effects of chronic hypoxia in vivo on the expression of human placental glucose transporter. Placenta 2006, 27, 49–55.
172. Jansson, T.; Wennergren, M.; Illsley, N.P. Glucose transporter protein expression in human placenta throughout gestation and in intrauterine growth retardation. J. Clin. Endocrinol. Metab. 1993, 77, 1554–1562.
173. Jansson, T.; Ylven, K.; Wennergren, M.; Powell, T.L. Glucose transport and system A activity in syncytiotrophoblast microvillous and basal plasma membranes in intrauterine growth restriction. Placenta 2002, 23, 392–399.
174. Glazier, J.D.; Cetin, I.; Perugino, G.; Ronzoni, S.; Grey, A.M.; Mahendran, D.; Marconi, A.M.; Pardi, G.; Sibley, C.P. 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, 514–519.
175. Mando, C.; Tabano, S.; Pileri, P.; Colapietro, P.; Marino, M.A.; Avagliano, L.; Doi, P.; Bulfamante, G.; Miozzo, M.; Cetin, I. Snat2 expression and regulation in human growth-restricted placentas. Pediatr. Res. 2013, 74, 104–110.
176. Jansson, T.; Scholtbach, V.; Powell, T.L. Placental transport of leucine and lysine is reduced in intrauterine growth restriction. Pediatr. Res. 1998, 44, 532–537.
177. Paolini, C.L.; Marconi, A.M.; Ronzoni, S.; di Noio, M.; Fennessey, P.V.; Pardi, G.; Battaglia, F.C. Placental transport of leucine, phenylalanine, glycine, and proline in intrauterine growth-restricted pregnancies. J. Clin. Endocrinol. Metab. 2001, 86, 5427–5432.
178. Ross, J.C.; Fennessey, P.V.; Wilkening, R.B.; Battaglia, F.C.; Meschia, G. Placental transport and fetal utilization of leucine in a model of fetal growth retardation. Am. J. Physiol. 1996, 270, 491–503.
179. Anderson, A.H.; Fennessey, P.V.; Meschia, G.; Wilkening, R.B.; Battaglia, F.C. Placental transport of threonine and its utilization in the normal and growth-restricted fetus. Am. J. Physiol. 1997, 272, 892–900.
180. De Vrijer, B.; Regnault, T.R.; Wilkening, R.B.; Meschia, G.; Battaglia, F.C. Placental uptake and transport of ACP, a neutral nonmetabolizable amino acid, in an ovine model of fetal growth restriction. Am. J. Physiol. Endocrinol. Metab. 2004, 287, 1114–1124.
181. Godfrey, K.M.; Matthews, N.; Glazier, J.; Jackson, A.; Wilman, C.; Sibley, C.P. Neutral amino acid uptake by the microvillous plasma membrane of the human placenta is inversely related to fetal size at birth in normal pregnancy. J. Clin. Endocrinol. Metab. 1998, 83, 3320–3326.
182. Nelson, D.M.; Smith, S.D.; Furesz, T.C.; Sadovsky, Y.; Ganapathy, V.; Parvin, C.A.; Smith, C.H. Hypoxia reduces expression and function of system A amino acid transporters in cultured term human trophoblasts. Am. J. Physiol. Cell Physiol. 2003, 284, 310–315.
183. Mishima, T.; Miner, J.H.; Morizane, M.; Stahl, A.; Sadovsky, Y. The expression and function of fatty acid transport protein-2 and -4 in the murine placenta. PLoS One 2011, 6, doi:10.1371/journal. pone.0025865.
184. Laivuori, H.; Gallaher, M.J.; Collura, L.; Crombleholme, W.R.; Markovic, N.; Rajakumar, A.; Hubel, C.A.; Roberts, J.M.; Powers, R.W. Relationships between maternal plasma leptin, placental leptin mRNA and protein in normal pregnancy, pre-eclampsia and intrauterine growth restriction without pre-eclampsia. Mol. Hum. Reprod. 2006, 12, 551–556.