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10 - Control of fetal metabolism: relevance to developmental origins of health and disease

Published online by Cambridge University Press:  08 August 2009

Abigail L. Fowden
Affiliation:
University of Cambridge
Janelle W. Ward
Affiliation:
University of Cambridge
Alison J. Forhead
Affiliation:
University of Cambridge
Peter Gluckman
Affiliation:
University of Auckland
Mark Hanson
Affiliation:
University of Southampton
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Summary

Introduction

Epidemiological observations in several human populations have shown that impaired growth in utero is associated with an increased risk of cardiovascular, metabolic and other diseases in later life (Barker 2001). Since the major determinant of fetal growth is the supply of nutrients to the fetus (Harding and Johnson 1995), these epidemiological associations have led to the hypothesis that adult disease originates in utero as a result of nutritional programming of tissues during early life. This hypothesis has been investigated experimentally in a number of species using a range of techniques to manipulate nutrient availability in the fetus (Table 10.1). These studies all support the hypothesis and show that the prenatal nutritional environment has long-term consequences for the offspring, even when there is little change in body weight. Hence, the factors controlling the fetal supply and utilisation of nutrients are important in the aetiology of adult disease. However, compared to postnatal metabolism, little is known about the programming of fetal metabolism per se. The aims of this review are, therefore, threefold: first, to consider the effects of varying nutrient availability on fetal metabolism; second, to examine the role of hormones in mediating these effects; and, finally, to discuss the mechanisms by which metabolic programming may occur in utero.

Nutritional regulation of fetal metabolism

The effects of varying nutrient availability on fetal metabolism depend on the specific nature of the nutritional challenge and on the duration, severity and gestational age at onset of the insult.

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Publisher: Cambridge University Press
Print publication year: 2006

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References

Aldoretta, P. W. and Hay, W. W. (1999). Effect of glucose supply on ovine uteroplacental glucose metabolism. Am. J. Physiol., 277, R947–58.Google ScholarPubMed
Apatu, R. S. K. and Barnes, R. J. (1991). Release of glucose from the liver of fetal and postnatal sheep by portal vein infusion of catecholamines or glucagon. J. Physiol., 436, 449–68.CrossRefGoogle ScholarPubMed
Asano, H., Han, V. K., Homan, J. and Richardson, B. S. (1997). Tissue DNA synthesis in the pre-term ovine fetus following 8 hours of sustained hypoxemia. J. Soc. Gynecol. Investig., 4, 236–40.CrossRefGoogle Scholar
Barker, D. J. P. (2001). The malnourished baby and infant. Br. Med. Bull., 60, 69–88.CrossRefGoogle ScholarPubMed
Barnes, R. J., Comline, R. S. and Silver, M. (1978). Effect of cortisol on liver glycogen concentrations in hypophysectomized, adrenalectomized and normal fetal lambs during late or prolonged gestation. J. Physiol., 275, 567–79.CrossRefGoogle ScholarPubMed
Bassett, J. M. and Hanson, C. (1998). Catecholamines inhibit growth in fetal sheep in the absence of hypoxemia. Am. J. Physiol., 274, R1536–45.Google ScholarPubMed
Bauer, M. K., Bernhard, H. B., Harding, J. E., Veldhuis, J. D. and Gluckman, P. D. (1995). The fetal somatotropic axis during long term maternal undernutrition in sheep: evidence for nutritional regulations in utero. Endocrinology, 136, 1250–7.CrossRefGoogle Scholar
Bauer, M. K., Harding, J. E., Bassett, N. S.et al. (1998). Fetal growth and placental function. Mol. Cell. Endocrinol., 140, 115–20.CrossRefGoogle ScholarPubMed
Bauer, M. K., Harding, J. E., Breier, B. H. and Gluckman, P. D. (2000). Exogenous GH infusion to late-gestational fetal sheep does not alter fetal growth and metabolism. J. Endocrinol., 166, 591–7.CrossRefGoogle Scholar
Bertram, C. E. and Hanson, M. A. (2001). Animal models and programming of metabolic syndrome. Br. Med. Bull., 60, 103–21.CrossRefGoogle ScholarPubMed
Bispham, J., Gopalakrishnan, G. C., Dandrea, J.et al. (2003). Maternal endocrine adaptation throughout pregnancy to nutrition manipulation: consequences for maternal plasma leptin and cortisol and the programming of fetal adipose tissue development. Endocrinology, 144, 3575–85.CrossRefGoogle ScholarPubMed
Boyle, D. W., Meschia, G. and Wilkening, R. B. (1992). Metabolism adaptation of fetal hindlimb to severe, nonlethal hypoxia. Am. J. Physiol., 263, R1130–5.Google Scholar
Budge, H., Edwards, L. J., McMillen, I. C.et al. (2004). Nutritional manipulation of fetal adipose tissue deposition and uncoupling protein 1 messenger RNA abundance in the sheep: differential effects of timing and duration. Biol. Reprod., 71, 359–65.CrossRefGoogle ScholarPubMed
Carver, T. D. and Hay, W. W. (1995). Uteroplacental carbon substrate metabolism and O2 consumption after long-term hypoglycemia in pregnant sheep. Am. J. Physiol., 269, E299–308.Google ScholarPubMed
Challis, J. R. G., Sloboda, D., Matthew, S. C.et al. (2002). Prostaglandins and the mechanisms of preterm birth. Reproduction, 124, 1–17.CrossRefGoogle ScholarPubMed
Clarke, K., Ward, J. W., Forhead, A. J., Giussani, D. A. and Fowden, A. L. (2002). Regulation of 11β hydroxysteroid dehydrogenase type 2 (11βHSD2) activity in ovine placenta by fetal cortisol. J. Endocrinol., 172, 527–34.CrossRefGoogle Scholar
Constancia, M., Hemberger, M., Hughes, J.et al. (2002). Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature, 417, 945–8.CrossRefGoogle ScholarPubMed
Currie, M. J., Bassett, N. S. and Gluckman, P. D. (1997). Ovine glucose transporter-1 and -3: cDNA partial sequences and developmental gene expression in the placenta. Placenta, 18, 393–401.CrossRefGoogle ScholarPubMed
Dalinghaus, M., Rudolph, C. D. and Rudolph, A. M. (1991). Effects of maternal fasting on hepatic glucogenesis and glucose metabolism in fetal lambs. J. Dev. Physiol., 16, 267–75.Google Scholar
Dandrea, J., Wilson, V., Gopalakrishnan, G.et al. (2001). Maternal nutritional manipulation of placental growth and glucose transporter 1 (GLUT-1) abundance in sheep. Reproduction, 122, 793–800.CrossRefGoogle Scholar
Das, U. G., Schroeder, R. E., Hay, W. W. and Devaskar, S. U. (1999). Time-dependent and tissue-specific effects of circulating glucose on fetal ovine glucose transporters. Am. J. Physiol., 276, R809–17.Google ScholarPubMed
Devaskar, S. U., Ganguli, S., Styer, D., Devaskar, U. P. and Sperling, M. (1984). Glucagon and glucose dynamics in sheep: evidence for glucagon reistance in the fetus. Am. J. Physiol., 246, E256–65.Google Scholar
DiGiacomo, J. E. and Hay, W. W. (1990). Fetal glucose metabolism and oxygen consumption during sustained maternal and fetal hypoglycaemia. Metabolism, 39, 139–202.CrossRefGoogle Scholar
Dodic, M., Moritz, K. and Wintour, E. M. (2003). Prenatal glucocoticoid exposure and adult disease. Arch. of Physiol. Biochem., 111, 61–9.CrossRefGoogle Scholar
Efstratiadis, A. (1998). Genetics of mouse growth. Int. J. Dev. Biol., 42, 955–76.Google ScholarPubMed
Ehrhardt, R. A. and Bell, A. W. (1975). Growth and metabolism of the ovine placenta during mid gestation. Placenta, 16, 727–41.CrossRefGoogle Scholar
Fahmi, A. I., Forhead, A. J., Fowden, A. L. and Vandenburg, J. I. (2004). Cortisol influences the ontogeny of both α- and β-subunits of the cardiac sodium channel in fetal sheep. J. Endocrinol., 180, 449–55.CrossRefGoogle ScholarPubMed
Fletcher, A. J. W., Gardner, D. S., Edwards, C. M. B., Fowden, A. L. and Giussani, D. A. (2003). Cardiovascular and endocrine responses to acute hypoxaemia during and following dexamethasone infusion in the ovine fetus. J. Physiol., 549, 271–87.CrossRefGoogle ScholarPubMed
Forhead, A. J., Thomas, L., Crabtree, J.et al. (2002). Plasma leptin concentration in fetal sheep during late gestation: ontogeny and effect of glucocorticoids. Endocrinology, 143, 1166–73.CrossRefGoogle ScholarPubMed
Forhead, A. J., Ousey, J. C., Allen, W. R. and Fowden, A. L. (2004). Postnatal insulin secretion and sensitivity after manipulation of fetal growth by embryo transfer in the horse. J. Endocrinol., 181, 459–67.CrossRefGoogle Scholar
Fowden, A. L. (1995). Endocrine regulation of fetal growth. Reprod. Fertil. Dev., 7, 351–63.CrossRefGoogle ScholarPubMed
Fowden, A. L. (2003). The insulin-like growth factors and feto-placental growth. Placenta, 24, 803–12.CrossRefGoogle ScholarPubMed
Fowden, A. L. and Forhead, A. J. (2001). The role of hormones in intrauterine development. In Lung Biology in Health & Disease (ed. Barker, D. J. P.). New York: Dekker, vol. 151, pp. 199–228.Google Scholar
Fowden, A. L. and Forhead, A. J. (2004). Endocrine mechanisms of intrauterine programming. Reproduction. 127, 515–26.CrossRefGoogle ScholarPubMed
Fowden, A. L. and Silver, M. (1995). The effects of thyroid hormones on oxygen and glucose metabolism in the sheep fetus during late gestation. J. Physiol., 482, 203–13.CrossRefGoogle ScholarPubMed
Fowden, A. L., Li, J. and Forhead, A. J. (1998a). Glucocorticoids and the preparation for life after birth: are there long-term consequences of the life insurance. Proc. Nutr. Soc., 57, 113–22.CrossRefGoogle Scholar
Fowden, A. L., Mundy, L. and Silver, M. (1998b). Developmental regulation of glucogenesis in the sheep fetus during late gestation. J. Physiol., 508, 937–47.CrossRefGoogle Scholar
Freemark, M., Keen, A., Fowlkes, J.et al. (1992). The placental lactogen receptor in maternal and fetal sheep liver: regulation by glucose and role in the pathogenesis of fasting during pregnancy. Endocrinology, 130, 1063–70.Google ScholarPubMed
Gardner, D. S., Fletcher, A. J. W., Fowden, A. L. and Giussani, D. A. (2001a). A novel method for controlled and reversible long term compression of the umbilical cord in fetal sheep. J. Physiol., 535, 217–29.CrossRefGoogle Scholar
Gardner, D. S., Fletcher, A. J. W., Fowden, A. L. and Giussani, D. A. (2001b). Adrenocorticotrophin and cortisol during umbilical cord compression and subsequent hypoxaemia in the late gestation ovine fetus. Endocrinology, 142, 589–98.CrossRefGoogle Scholar
Gardner, D. S., Giussani, D. A. and Fowden, A. L. (2003). Hindlimb glucose and lactate metabolism during umbilical cord compression and acute hypoxemia in the late-gestation ovine fetus. Am. J. Physiol. Regul. Integr. Comp. Physiol., 284, R954–64.CrossRefGoogle ScholarPubMed
Gluckman, P. D. and Pinal, C. S. (2002). Maternal–placental– fetal interactions in the endocrine regulation of fetal growth. Endocrine, 19, 81–9.CrossRefGoogle ScholarPubMed
Godfrey, K. M., Matthews, N., Glazier, J., Jackson, A., Wilman, C. and Sibley, C. P. (1998). Neutral amino acid uptake by the microvillous membrane of human placenta is inversely related to fetal size at birth in normal pregnancy. J. Clin. Endocrinol. Metab., 83, 3320–6.Google ScholarPubMed
Hahn, T., Barth, S., Graf, R.et al. (1999). Placental glucose transport expression is regulated by glucocorticoids. J.Clin. Endorcinol. Metab., 84, 1445–52.Google ScholarPubMed
Harding, J. E. and Johnson, B. (1995). Nutrition and fetal growth. Reprod. Fertil. Dev., 7, 538–47.CrossRefGoogle ScholarPubMed
Harding, J. E., Liu, L., Evans, P. C. and Gluckman, P. D. (1994). Insulin-like growth factor 1 alters feto-placental protein and carbohydrate metabolism in fetal sheep. Endocrinology. 134, 1509–14.CrossRefGoogle ScholarPubMed
Harding, J. E., Evans, P. C. and Gluckman, P. D. (1997). Maternal growth hormone treatment increases placental diffusion capacity but not fetal or placental growth in sheep. Endocrinology, 138, 5352–8.CrossRefGoogle Scholar
Hawkins, P., Steyn, C., McGarrigle, H. H.et al. (2000). Cardiovascular and HPA axis development in late gestation fetal sheep and young lambs following modest maternal nutrient restriction in early gestation. Reprod. Fertil. Dev., 12, 443–56.CrossRefGoogle Scholar
Hay, W. W. (1995). Regulation of placental metabolism by glucose supply. Reprod. Fertil. Dev., 7, 365–75.CrossRefGoogle ScholarPubMed
Hay, W. W., Sparks, J. W., Wilkening, R. B., Battaglia, F. C. and Meschia, G. (1984). Fetal glucose uptake and utilization as functions of maternal glucose concentration. Am. J. Physiol., 246, E237–42.Google ScholarPubMed
Hay, W. W., DiGiacomo, J. E., Meznarich, H. K., Hirst, K. and Zerbe, G. (1989). Effects of glucose and insulin on fetal glucose oxidation and oxygen consumption. Am. J. Physiol., 256, E704–13.Google ScholarPubMed
Hendrich, C. E. and Porterfield, S. P. (1996). Ribosomal protein synthesis in 16 and 19 day gestation fetuses of hypothyroid mothers. Proc. Soc. Exp. Biol. Med., 213, 273–80.CrossRefGoogle Scholar
Holemans, K , Aerts, L. and Assche, F. A. (2003). Fetal growth retardation and consequences for the offspring in animal models. J. Soc. Gynecol. Investig., 10, 392–9.CrossRefGoogle ScholarPubMed
Hooper, S. B., Walker, D. W. and Harding, R. (1995). Oxygen, glucose, and lactate uptake by fetus and placenta during prolonged hypoxemia. Am. J. Physiol., 268, 303–9.Google ScholarPubMed
Hyatt, M. A., Walker, D. A., Stephenson, T. and Symonds, M. E. (2004). Ontogeny and nutritional manipulation of the hepatic prolactin–growth hormone–insulin-like growth factor axis in the ovine fetus and in neonate and juvenile sheep. Proc. Nutr. Soc., 63, 127–35.CrossRefGoogle ScholarPubMed
Jacobs, R., Owens, J. A., Falconer, J., Webster, M. E. D. and Robinson, J. S. (1988a). Changes in metabolic concentrations in fetal sheep subjected to prolonged hypobaric hypoxia. J. Dev. Physiol., 10, 113–25.Google Scholar
Jacobs, R., Robinson, J. S., Owens, J. A., Falconer, J. and Webster, M. E. D. (1988b). The effect of prolonged hypobaric hypoxia on growth of fetal sheep. J. Dev. Physiol., 10, 97–112.Google Scholar
Jenkinson, C. M. C., Min, S. H., Mackenzie, D. D. S., McCutcheon, S. N., Brier, B. H. and Gluckman, P. D. (1999). Placental development and fetal growth in growth hormone-treated ewes. Growth Horm. IGF Res., 9, 11–17.CrossRefGoogle ScholarPubMed
Jensen, E. C., Harding, J. E., Bauer, M. K. and Gluckman, P. D. (1999). Metabolic effects of IGF-I in the growth retarded fetal sheep. J. Endocrinol., 161, 485–94.CrossRefGoogle ScholarPubMed
Jensen, E. C., Gallaher, B. W., Brier, B. H. and Harding, J. E. (2002). The effect of a chronic maternal cortisol infusion on the late-gestation fetal sheep. J. Endocrinol., 174, 27–36.CrossRefGoogle ScholarPubMed
Johnson, J. D. and Dunham, T. (1988). Protein turnover in tissues of the fetal rat after prolonged maternal malnutrition. Pediatr. Res., 23, 534–8.CrossRefGoogle ScholarPubMed
Jones, C. T. (1991). Control of glucose metabolism in the perinatal period. J. Dev. Physiol., 15, 81–9.Google ScholarPubMed
Kamitomo, M., Onishi, J., Gutierrez, I., Stiffel, V. M. and Gilbert, R. D. (2002). Effects of long-term hypoxia and development on cardiac contractile proteins in fetal and adult sheep. J. Soc. Gynecol. Investig., 9, 335–41.CrossRefGoogle ScholarPubMed
Kaneta, M., Liechty, E. A., Moorehead, H. C. and Lemons, J. A. (1991). Ovine fetal and maternal glycogen during fasting. Biol. Neonate, 60, 215–20.CrossRefGoogle ScholarPubMed
Kelly, R. W. (1992). Nutrition and placental development. Proc. Nutr. Soc. Aust., 17, 203–11.Google Scholar
Krebs, C., Longo, L. D. and Leiser, R. (1997). Term ovine placental vasculature: comparisons of sea level and high altitude conditions by corrosion. Placenta, 18 43–51.CrossRefGoogle Scholar
Lemons, J. A. and Schreiner, R. L. (1983). Amino acid metabolism in the ovine fetus. Am. J. of Physiol., 244, E459–66.Google ScholarPubMed
Lemons, J. A. and Schreiner, R. L. (1984). Metabolic balance of the ovine fetus during the fed and fasted states. Ann. Nutr. Metab., 28, 268–280.CrossRefGoogle ScholarPubMed
Lemons, J. A. and Snodgrass, P. J. (1986). Effect of maternal fast on the urea cycle enzymes of the ovine fetus. J. Pediatr. Gastroenterol. Nutr., 5, 138–42.CrossRefGoogle ScholarPubMed
Lemons, J. A., Moorehead, A. C. and Hage, G. (1986). Effects of fasting on gluconeogenic enzymes in the ovine fetus. Pediatr. Res., 20, 676–9.CrossRefGoogle ScholarPubMed
Lesage, J., Hahn, D., Lyonhardt, M., Blondeau, B., Bryant, B. and Dupouy, J. P. (2002). Maternal undernutrition during late gestation-induced intrauterine growth restriction in the rat is associated with impaired placental GLUT3 expression, but does nor correlate with endogenous corticosterone levels. J. Endocrinol., 174, 37–43.CrossRefGoogle ScholarPubMed
Leury, B. J., Chandler, K. D., Bird, A. R. and Bell, A. W. (1990). Effects of maternal undernutrition and exercise on glucose kinetics in fetal sheep. Br. J. Nutr., 64, 463–72.CrossRefGoogle ScholarPubMed
Levitsky, L., Paton, J. B. and Fisher, D. E. (1988). Precursors to glycogen in ovine fetuses. Am. J. Physiol., 255, E743–7.Google ScholarPubMed
Levitsky, L. L., Stonesweet, B. S., Mink, R. and Zheng, Q. (1993). Glutamine carbon disposal and net glutamine uptake in fetuses of fed and fasted ewes. Am. J. Physiol., 265, E722–7.Google ScholarPubMed
Liechty, E. A. and Lemons, A. J. (1984). Changes in ovine fetal hindlimb amino acid metabolism during maternal fasting. Am. J. Physiol., 246, E430–5.Google ScholarPubMed
Liechty, E. A., Barone, S. and Nutt, M. (1987). Effect of maternal fasting on ovine fetal and maternal branched-chain amino acid transaminase activities. Biol. Neonate, 52, 166–73.CrossRefGoogle ScholarPubMed
Liechty, E. A., Boyle, D. W., Moorehead, H., Liu, Y. M. and Denne, S. C. (1992). Effect of hyperinsulinemia on ovine fetal leucine kinetics during prolonged maternal fasting. Am. J. Physiol., 263, E696–702.Google ScholarPubMed
Liechty, E. A., Boyle, D. W., Moorehead, H., Lee, W- H., Bowsher, R. R. and Denne, S. C. (1996). Effects of circulating IGF-I on glucose and amino acid kinetics in the ovine fetus. Am. J. Physiol., 271, E177–85.Google ScholarPubMed
Limesand, S. W. and Hay, W. W. (2003). Adaptation of ovine fetal pancreatic insulin secretion to chronic hypoglycaemia and euglycaemic correction. J. Physiol., 547, 95–105.CrossRefGoogle ScholarPubMed
Liu, L., Harding, J. E., Evans, P. C. and Gluckman, P. D. (1994). Maternal insulin-like growth factor-I infusion alters feto-placental carbohydrate and protein metabolism in pregnant sheep. Endocrinology, 135, 895–900.CrossRefGoogle ScholarPubMed
Lorijn, R. H. W., Nelson, J. C. and Longo, L. D. (1980). Induced fetal hyperthyroidism: cardiac output and oxygen consumption. Am. J. Physiol., 239, H302–7.Google ScholarPubMed
Lueder, F. L., Kim, S. B., Buroker, C. A., Bangalore, S. A. and Ogata, E. S. (1995). Chronic maternal hypoxia retards fetal growth and increases glucose utilization of select fetal tissues in the rat. Metabolism 44, 532–7.CrossRefGoogle ScholarPubMed
Lumey, L. H. (1998). Compensatory placental growth after restricted maternal nutrition in early pregnancy. Placenta, 19, 105–11.Google ScholarPubMed
McCrabb, G. J., Egan, A. R. and Hosking, B. J. (1991). Maternal undernutrition during mid-pregnancy in sheep: placental size and its relationship to calcium transfer during late pregnancy. Br. J. Nutr., 65, 157–68.CrossRefGoogle ScholarPubMed
McLellan, K. C., Bocking, A. D., White, S. E. and Han, V. K. M. (1995). Placental and fetal hepatic growth are selectively inhibited by prolonged reductions of uterine blood flow in pregnant sheep. Reprod. Fertil. Dev., 7, 405–10.CrossRefGoogle ScholarPubMed
Mellor, D. J. and Murray, L. (1985). Effects of maternal nutrition on the availability of energy in the body reserves of fetuses at term and in colostrum from Scottish blackface ewes with twin lambs. Res. Vet. Sci., 3, 235–40.Google Scholar
Milley, J. R. (1987). Protein synthesis during hypoxia in fetal lambs. Am. J. Physiol., 252, E519–24.Google ScholarPubMed
Milley, J. R. (1988). Uptake of exogenous substrates during hypoxia in fetal lambs. Am. J. Physiol., 254, E572–8.Google ScholarPubMed
Milley, J. R. (1994). Effects of insulin on ovine fetal leucine kinetics and protein metabolism. J. Clin. Investig., 93, 1616–24.CrossRefGoogle ScholarPubMed
Milley, J. R. (1995). Effects of increased cortisol concentration on ovine fetal leucine kinetics and protein metabolism. Am. J. Physiol., 268, E1114–22.Google ScholarPubMed
Milley, J. R. (1996). Fetal substrate uptake during increased ovine fetal cortisol concentration. Am. J. Physiol., 271, E186–91.Google ScholarPubMed
Milley, J. R. (1997). Ovine fetal metabolism during norepinephrine infusion. Am. J. Physiol., 273, E336–47.Google ScholarPubMed
Milley, J. R. (1998). Ovine fetal leucine kinetics and protein metabolism during the decreased oxygen availability. Am. J. Physiol., 274, E618–26.Google ScholarPubMed
Nakamura, K., Stokes, J. B. and McCray, P. B. (2002). Endogenous and exogenous glucocorticoid regulation of ENaC mRNA expression in developing kidney and lung. Am. J. Physiol. Cell Physiol., 283, C762–72.CrossRefGoogle Scholar
Oliver, M. H., Hawkins, P., Breier, B. H., Vanzul, P. L., Sargison, S. A. and Harding, J. E. (2001). Maternal undernutrition during the periconceptual period increases plasma taurine levels and insulin response to glucose but not arginine in the late gestation fetal sheep. Endocrinology, 142, 4576–9.CrossRefGoogle ScholarPubMed
Osgerby, J. C., Wathes, D. C., Howard, D. and Gadd, T. S. (2004). The effect of maternal undernutrition on the placental growth trajectory and the uterine insulin-like growth factor axis in the pregnant ewe. J. Endocrinol., 182, 89–103.CrossRefGoogle ScholarPubMed
Ozanne, S. E. (2001). Metabolic programming in animals. Br. Med. Bull., 60, 143–52.CrossRefGoogle ScholarPubMed
Ozanne, S. E., Nave, B. T., Wang, C. L., Shepherd, R. P., Prins, J. and Smith, G. D. (1997). Poor fetal nutrition causes long-term changes in expression of insulin signaling components in adipocytes. Am. J. Physiol., 273, E46–51.Google ScholarPubMed
Penninga, L. and Longo, L. D. (1998). Ovine placentome morphology: effect of high altitude, long-term hypoxia. Placenta, 19, 187–93.CrossRefGoogle ScholarPubMed
Peterside, I. E., Selak, M. A. and Simmons, R. A. (2003). Impaired oxidative phosphorylation in hepatic mitochondria in growth-retarded rats. Am. J. Physiol. Endocrinol. Metal., 285, E1258–66.CrossRefGoogle ScholarPubMed
Pham, T. D., MacLennan, N. K., Chiu, C. T., Laksana, G. S., Hsu, J. L. and Lane, R. H. (2003). Uteroplacental insufficiency increases apoptosis and alters p53 gene methylation in the full-term IUGR rat kidney. Am. J. Physiol. Regul. Integr. Comp. Physiol., 285, R962–70.CrossRefGoogle ScholarPubMed
Philipps, A. F., Rosenkrantz, T. S., Lemons, J. A., Knox, I., Porte, P. J. and Raye, J. R. (1990). Insulin-induced alterations in amino acid metabolism in the fetal lamb. J. Dev. Physiol., 13, 251–9.Google ScholarPubMed
Price, W. A., Rong, L., Stiles, A. D. and Ercole, A. J. (1992). Changes in IGF-I and -II, IGF binding protein, and IGF receptor transcript abundance after uterine artery ligation. Pediatr. Res., 32, 291–5.CrossRefGoogle ScholarPubMed
Rae, M. T., Rhind, S. M., Kyle, C. E., Miller, D. W. and Brooks, A. N. (2002). Maternal undernutrition alters triiodothyronine concentration and pituitary response to GnRH in fetal sheep. J. Endocrinol., 173, 449–55.CrossRefGoogle Scholar
Rees, W. D., Hay, S. M., Brown, D. S., Antipatis, C. and Palmer, R. M. (2000). Maternal protein deficiency causes hypermethylation of DNA in the livers of rat fetuses. J. Nutr., 130, 1821–26.CrossRefGoogle ScholarPubMed
Reik, W., Constancia, M., Fowden, A.et al. (2003). Regulation of supply and demand for maternal nutrients in mammals by imprinted genes. J. Physiol., 547, 35–44.CrossRefGoogle ScholarPubMed
Richardson, B. S. and Bocking, A. D. (1998). Metabolic and circulatory adaptations to chronic hypoxia in the fetus. Comp. Biochem. Physiol. A Mol. Integr. Physiol., 119, 717–23.CrossRefGoogle ScholarPubMed
Roberts, C. T., Sohlstrom, A., Kind, K. L.et al. (2001). Maternal food restriction reduces the exchange surface area and increases the barrier thickness of the placenta in the guinea-pig. Placenta, 22, 177–85.CrossRefGoogle ScholarPubMed
Rosato, R. R., Jahn, G. A. and Gimenez, M. S. (1992). Amelioration of some metabolic effects produced by hyperthyroidism in late pregnant rats and their fetuses: effects on lipids and proteins. Horm. Metab. Res., 24, 15–20.CrossRefGoogle ScholarPubMed
Rudolph, C. D., Roman, C. and Rudolph, A. M. (1989). Effect of acute umbilical cord compression on hepatic carbohydrate metabolism in the fetal lamb. Pediatr. Res., 25, 228–33.CrossRefGoogle ScholarPubMed
Sibley, C. P., Coan, P. M., Ferguson-Smith, A. C.et al. (2004). Placental-specific insulin-like growth factor 2 (Igf2) regulates the diffusional exchange characteristics of the mouse placenta. Proc. Nat. Acad. Sci. USA, 101, 8204–8.CrossRefGoogle ScholarPubMed
Simmons, M. A., Meschia, G., Makowski, E. L. and Battaglia, F. C. (1974). Fetal metabolic response to maternal starvation. Pediatr. Res., 8, 830–36.CrossRefGoogle ScholarPubMed
Sparre, T., Reusens, B., Cherif, H.et al. (2003). Intrauterine programming of fetal islet gene expression in rats: effects of maternal protein restriction during gestation revealed by proteome analysis. Diabetologia, 46, 1497–511.CrossRefGoogle ScholarPubMed
Sperling, M. A., Ganguli, S., Leslie, N. and Landt, K. (1984). Fetal–perinatal catecholamine secretion: role in perinatal glucose homeostasis. Am. J. Physiol., 247, E69–74.Google ScholarPubMed
Steyn, C., Hawkins, P., Saito, T., Noakes, D. E., Kingdom, J. P. C. and Hanson, M. A. (2001). Undernutrition during the first half of gestation increases the predominance of fetal tissue in late-gestation ovine placentomes. Eur. J. Obstet. Gynecol. Reprod. Biol., 98, 165–70.CrossRefGoogle ScholarPubMed
Stratford, L. L. and Hooper, S. B. (1997). Effect of hypoxemia on tissue glycogen content and glycolytic enzyme activities in fetal sheep. Am. J. Physiol., 241, R103–10.Google Scholar
Symonds, M. E., Gopalakrishnan, G., Bispham, J.et al. (2003). Maternal nutrient restriction during placental growth, programming of fetal adiposity and juvenile blood pressure control. Arch. Physiol. Biochem., 111, 45–52.CrossRefGoogle ScholarPubMed
Teng, C., Battaglia, F. C., Meschia, G., Narkewicz, M. R., and Wilkening, R. B. (2002). Fetal hepatic and umbilical uptakes of glucogenic substrates during a glucagon–somatostatin infusion. Am. J. Physiol. Endocrinol. Metab., 282, E542–50.CrossRefGoogle ScholarPubMed
Townsend, S. F., Rudolph, C. D. and Rudolph, A. M. (1991). Cortisol induces perinatal hepatic gluconeogenesis in the lamb. J. Dev. Physiol., 16, 71–9.Google ScholarPubMed
Walker, V., Gentry, A. J., Green, L. R., Hanson, M. A. and Bennet, L. (2000). Effects of hypoxia on plasma amino acids of fetal sheep. Amino Acids, 18, 146–56.CrossRefGoogle ScholarPubMed
Ward, J. W., Wooding, F. B. P. and Fowden, A. L. (2002). The effects of cortisol on the binucleate cell population in the ovine placenta during late gestation. Placenta, 23, 451–8.CrossRefGoogle ScholarPubMed
Ward, J. W., Wooding, F. B. P. and Fowden, A. L. (2004). Ovine feto-placental metabolism. J. Physiol., 554, 529–41.CrossRefGoogle ScholarPubMed
Whorwood, C. B., Firth, K. M., Budge, H. and Symonds, M. E. (2001). Maternal undernutrition during early to midgestation programs tissue-specific alterations in the expression of the glucocorticoid receptor, 11β-hydroxysteroid dehydrogenase isoforms, and type1 angiotensin II receptor in neonatal sheep. Endocrinology, 142, 2854–64.CrossRefGoogle Scholar
Yang, K., Shearman, K., Asano, H. and Richardson, B. S. (1997). The effects of hypoxemia on 11 beta-hydroxysteroid dehydrogenase types 1 and 2 gene expression in preterm fetal sheep. J. Soc. Gynecol. Investig., 4, 124–9.CrossRefGoogle ScholarPubMed
Young, L. E. (2001). Imprinted genes and the Barker hypothesis. Twins Res., 4, 307–17.CrossRefGoogle ScholarPubMed
Young, M., Stern, D. R., Horn, J. and Noakes, D. E. (1982). Protein synthetic rate in the sheep placenta in vivo: the influence of insulin. Placenta, 3, 159–64.CrossRefGoogle ScholarPubMed

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