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Assessment of Placental Transport Function in Studies of Disease Programming

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Investigations of Early Nutrition Effects on Long-Term Health

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1735))

Abstract

Environmental conditions during pregnancy affect fetal growth and development and program the offspring for poor future health. These effects may be mediated by the placenta, which develops to transfer nutrients from the mother to the fetus for growth. The ability to measure the unidirectional maternofetal transfer of non-metabolizable radio-analogues of glucose and amino acid by the placenta in vivo has thus been invaluable to our understanding of the regulation of fetal growth, particularly in small animal models. Herein, I describe the method by which in vivo placental transfer function can be quantified in the mouse, an animal model widely used in studies of in utero disease programming.

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References

  1. Sibley CP (2009) Understanding placental nutrient transfer - why bother? New biomarkers of fetal growth. J Physiol 587(14):3431–3440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lager S, Powell TL (2012) Regulation of nutrient transport across the placenta. J Pregnancy 2012:179827. https://doi.org/10.1155/2012/179827

    Article  PubMed  PubMed Central  Google Scholar 

  3. Dimasuay KG, Boeuf P, Powell TL, Jansson T (2016) Placental responses to changes in the maternal environment determine fetal growth. Front Physiol 7:12. https://doi.org/10.3389/fphys.2016.00012

    Article  PubMed  PubMed Central  Google Scholar 

  4. Sferruzzi-Perri AN, Camm EJ (2016) The programming power of the placenta. Front Physiol 7:33. https://doi.org/10.3389/fphys.2016.00033

    Article  PubMed  PubMed Central  Google Scholar 

  5. Sferruzzi-Perri AN, Sandovici I, Constancia M, Fowden AL (2017) Placental phenotype and the insulin-like growth factors: resource allocation to fetal growth. J Physiol 595:5057–5093

    Article  CAS  PubMed  Google Scholar 

  6. Lewis RM, Cleal JK, Hanson MA (2012) Review: placenta, evolution and lifelong health. Placenta 33(Suppl):S28–S32

    Article  PubMed  Google Scholar 

  7. Fowden AL, Sferruzzi-Perri AN, Coan PM, Constancia M, Burton GJ (2009) Placental efficiency and adaptation: endocrine regulation. J Physiol 587(14):3459–3472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sibley CP, Brownbill P, Dilworth M, Glazier JD (2010) Review: adaptation in placental nutrient supply to meet fetal growth demand: implications for programming. Placenta 31(Suppl):S70–S77

    Article  PubMed  Google Scholar 

  9. Sferruzzi-Perri AN, Lopez-Tello J, Fowden AL, Constancia M (2016) Maternal and fetal genomes interplay through phosphoinositol 3-kinase(PI3K)-p110a signalling to modify placental resource allocation. Proc Natl Acad Sci U S A 113(40):11255–11260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhang S, Regnault TR, Barker PL, Botting KJ, McMillen IC, McMillan CM et al (2015) Placental adaptations in growth restriction. Forum Nutr 7(1):360–389

    CAS  Google Scholar 

  11. Diaz P, Powell TL, Jansson T (2014) The role of placental nutrient sensing in maternal-fetal resource allocation. Biol Reprod 91(4):82. https://doi.org/10.1095/biolreprod.114.121798

    Article  PubMed  PubMed Central  Google Scholar 

  12. Atkinson DE, Robinson NR, Sibley CP (1991) Development of passive permeability characteristics of rat placenta during the last third of gestation. Am J Phys 261(6 Pt 2):R1461–R1464

    CAS  Google Scholar 

  13. Sferruzzi-Perri AN, Owens JA, Standen P, Taylor RL, Heinemann GK, Robinson JS et al (2007) Early treatment of the pregnant guinea pig with IGFs promotes placental transport and nutrient partitioning near term. Am J Physiol Endocrinol Metab 292(3):E668–E676

    Article  CAS  PubMed  Google Scholar 

  14. Jansson N, Pettersson J, Haafiz A, Ericsson A, Palmberg I, Tranberg M et al (2006) Down-regulation of placental transport of amino acids precede the development of intrauterine growth restriction in rats fed a low protein diet. J Physiol 576(3):935–946

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Sferruzzi-Perri AN, Owens JA, Standen P, Taylor RL, Robinson JS, Roberts CT (2007) Early pregnancy maternal endocrine IGF-I programs the placenta for increased functional capacity throughout gestation. Endocrinology 148(9):4362–4370

    Article  CAS  PubMed  Google Scholar 

  16. Jones HN, Woollett LA, Barbour N, Prasad PD, Powell TL, Jansson T (2008) High-fat diet before and during pregnancy causes marked up-regulation of placental nutrient transport and fetal overgrowth in C57/BL6 mice. FASEB J 23(1):271–278

    Article  PubMed  Google Scholar 

  17. Constancia M, Angiolini E, Sandovici I, Smith P, Smith R, Kelsey G et al (2005) 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 102(52):19219–19224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sferruzzi-Perri AN, Vaughan OR, Coan PM, Suciu MC, Darbyshire R, Constancia M et al (2011) Placental-specific Igf2 deficiency alters developmental adaptations to undernutrition in mice. Endocrinology 152(8):3202–3212

    Article  CAS  PubMed  Google Scholar 

  19. Sferruzzi-Perri AN, Vaughan OR, Haro M, Cooper WN, Musial B, Charalambous M et al (2013) An obesogenic diet during mouse pregnancy modifies maternal nutrient partitioning and the fetal growth trajectory. FASEB J 27(10):3928–3937

    Article  CAS  PubMed  Google Scholar 

  20. Higgins JS, Vaughan OR, de Liger EF, Fowden AL, Sferruzzi-Perri AN (2015) Placental phenotype and resource allocation to fetal growth are modified by the timing and degree of hypoxia during mouse pregnancy. J Physiol 594(5):1341–1356

    Article  PubMed  PubMed Central  Google Scholar 

  21. Coan PM, Angiolini E, Sandovici I, Burton GJ, Constância M, Fowden AL (2008) Adaptations in placental nutrient transfer capacity to meet fetal growth demands depend on placental size in mice. J Physiol 586(18):4567–4576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Coan PM, Vaughan OR, McCarthy J, Mactier C, Burton GJ, Constância M et al (2011) Dietary composition programmes placental phenotype in mice. J Physiol 589(14):3659–3670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Coan PM, Vaughan OR, Sekita Y, Finn SL, Burton GJ, Constancia M et al (2010) Adaptations in placental phenotype support fetal growth during undernutrition of pregnant mice. J Physiol 588(3):527–538

    Article  CAS  PubMed  Google Scholar 

  24. Ganguly A, Collis L, Devaskar SU (2012) Placental glucose and amino acid transport in calorie-restricted wild-type and Glut3 null heterozygous mice. Endocrinology 153(8):3995–4007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Varma DR, Ramakrishnan R (1991) Effects of protein-calorie malnutrition on transplacental kinetics of aminoisobutyric-acid in rats. Placenta 12(3):277–284

    Article  CAS  PubMed  Google Scholar 

  26. Wyrwoll CS, Seckl JR, Holmes MC (2009) Altered placental function of 11{beta}-hydroxysteroid dehydrogenase 2 knockout mice. Endocrinology 150(3):1287–1293

    Article  CAS  PubMed  Google Scholar 

  27. Vaughan OR, Fisher HM, Dionelis KN, Jefferies EC, Higgins JS, Musial B et al (2015) Corticosterone alters materno-fetal glucose partitioning and insulin signalling in pregnant mice. J Physiol 593(5):1307–1321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Vaughan OR, Sferruzzi-Perri AN, Coan PM, Fowden AL (2013) Adaptations in placental phenotype depend on route and timing of maternal dexamethasone administration in mice. Biol Reprod 89(4):1–12

    Article  Google Scholar 

  29. Vaughan OR, Sferruzzi-Perri AN, Fowden AL (2012) Maternal corticosterone regulates nutrient allocation to fetal growth in mice. J Physiol 590(21):5529–5540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Jansson T, Persson E (1990) Placental transfer of glucose and amino acids in intrauterine growth retardation: studies with substrate analogs in the awake guinea pig. Pediatr Res 28(3):203–208

    Article  CAS  PubMed  Google Scholar 

  31. Audette MC, Challis JR, Jones RL, Sibley CP, Matthews SG (2011) Antenatal dexamethasone treatment in midgestation reduces system A-mediated transport in the late-gestation murine placenta. Endocrinology 152(9):3561–3570

    Article  CAS  PubMed  Google Scholar 

  32. Vaughan OR, Phillips HM, Everden AJ, Sferruzzi-Perri AN, Fowden AL (2015) Dexamethasone treatment of pregnant F0 mice leads to parent of origin-specific changes in placental function of the F2 generation. Reprod Fertil Dev 27(4):704–711

    Article  CAS  PubMed  Google Scholar 

  33. Dilworth MR, Kusinski LC, Cowley E, Ward BS, Husain SM, Constância M et al (2010) Placental-specific Igf2 knockout mice exhibit hypocalcemia and adaptive changes in placental calcium transport. Proc Natl Acad Sci U S A 107(8):3894–3899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Flexner LB, Pohl HA (1941) Transfer of radioactive sodium across the placenta of the guinea pig. J Physiology 132:594–606

    CAS  Google Scholar 

  35. Stulc J, Stulcova B (1986) Transport of calcium by the placenta of the rat. J Physiol 371:1–16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bond H, Dilworth MR, Baker B, Cowley E, Requena Jimenez A, Boyd RD et al (2008) Increased maternofetal calcium flux in parathyroid hormone-related protein-null mice. J Physiol 586(7):2015–2025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Sibley CP, Coan PM, Ferguson-Smith AC, Dean W, Hughes J, Smith P et al (2004) Placental-specific insulin-like growth factor 2 (Igf2) regulates the diffusional exchange characteristics of the mouse placenta. Proc Natl Acad Sci U S A 101(21):8204–8208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Adams AK, Reid DL, Thornburg KL, Faber JJ (1988) In vivo placental permeability to hydrophilic solutes as a function of fetal weight in the guinea pig. Placenta 9(4):409–416

    Article  CAS  PubMed  Google Scholar 

  39. Stulc J (1997) Placental transfer of inorganic ions and water. Physiol Rev 77(3):805–836

    Article  CAS  PubMed  Google Scholar 

  40. Cramer S, Beveridge M, Kilberg M, Novak D (2002) Physiological importance of system A-mediated amino acid transport to rat fetal development. Am J Physiol Cell Physiol 282(1):C153–C160

    Article  CAS  PubMed  Google Scholar 

  41. Coan PM, Ferguson-Smith AC, Burton GJ (2004) Developmental dynamics of the definitive mouse placenta assessed by stereology. Biol Reprod 70(6):1806–1813

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Amanda N. Sferruzzi-Perri .

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Sferruzzi-Perri, A.N. (2018). Assessment of Placental Transport Function in Studies of Disease Programming. In: Guest, P. (eds) Investigations of Early Nutrition Effects on Long-Term Health. Methods in Molecular Biology, vol 1735. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7614-0_14

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  • DOI: https://doi.org/10.1007/978-1-4939-7614-0_14

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7613-3

  • Online ISBN: 978-1-4939-7614-0

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