Skip to main content

Advertisement

SpringerLink
Log in

In Utero Development of Fetal Thirst and Appetite: Potential for Programming

  • Review
  • Published:
The Journal of the Society for Gynecologic Investigation: JSGI Aims and scope Submit manuscript

Abstract

Thirst and appetite-mediated ingestive behavior develop and are likely programmed in utero, thus preparing for newborn and adult ingestive behavior. Fetal swallowing activity is markedly different from that of the adult, as spontaneous fetal swallowing occurs at a markedly (six-fold) higher rate compared with spontaneous adult drinking activity. This high rate of fetal swallowing is critical for the regulation of amniotic fluid volume and the development of the fetal gastrointestinal tract. Disordered fetal swallowing has been associated with both a decrease (oligohydramnios) and increase (polyhydramnios) in amniotic fluid volume. Both conditions are associated with a significant increase in perinatal morbidity and mortality, and limited treatment modalities are currently available. The mechanisms underlying the high rate of human fetal swallowing are regulated, in part, by tonic activity of central angiotensin II, glutamate N-methyl-D-aspartate receptors, and neuronal nitric oxide synthase. Fetal hypertonicity-mediated dipsogenesis is likely programmed in utero, as offspring of water-restricted ewes demonstrate a programmed syndrome of plasma hypertonicity, with significant hematologic and cardiovascular alterations. Similar to dipsogenic mechanisms, peripheral and central fetal orexic mechanisms also develop in utero, as demonstrated by increased fetal swallowing after both oral sucrose infusion and central injection of neuropeptide Y. The role of leptin in regulating fetal ingestive behavior is interesting because, contrary to actions in adults, leptin does not suppress fetal ingestive behavior. Teleologically, this may be of value during the newborn period, as unopposed appetite stimulatory mechanisms may facilitate rapid fetal and newborn weight gain. An adverse intrauterine environment, with altered fetal orexic factors during the critical developmental period of fetal life, may alter the normal setpoints of appetitive behavior and potentially lead to programming of adulthood hyperphagia and obesity. Further research is needed to delineate the mechanistic relationship between the intrauterine environment and the development of the setpoints of adult appetite and thirst.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Petrikovsky BM, Schifrin B, Diana L. The effect of fetal acoustic stimulation on fetal swallowing and amniotic fluid index. Obstet Gynecol 1993;81(4):548–50.

    CAS  PubMed  Google Scholar 

  2. Fujino Y, Agnew CL, Schreyer P, Ervin MG, Sherman DJ, Ross MG. Amniotic fluid volume response to esophageal occlusion in fetal sheep. Am J Obstet Gynecol 1991;165(6 Pt 1):1620–6.

    Article  CAS  PubMed  Google Scholar 

  3. Kimble RM, Harding JE, Kolbe A. Does gut atresia cause polyhydramnios? Pediatr Surg Int 1998;13(2–3):115–7.

    Article  CAS  PubMed  Google Scholar 

  4. Brace RA, Wlodek ME, Cock ML, Harding R. Swallowing of lung liquid and amniotic fluid by the ovine fetus under normoxic and hypoxic conditions. Am J Obstet Gynecol 1994;171(3):764–70.

    Article  CAS  PubMed  Google Scholar 

  5. Trahair JF, Harding R. Restitution of swallowing in the fetal sheep restores intestinal growth after midgestation esophageal obstruction. J Pediatr Gastroenterol Nutr 1995;20(2):156–61.

    Article  CAS  PubMed  Google Scholar 

  6. Mulvihill J, Stone M, Fonkalsrud EW. Trophic effect of amniotic fluid on fetal gestational development. J Surg Res 1986;40:291–6.

    Article  CAS  PubMed  Google Scholar 

  7. Mulvihill SJ, Stone MM, Fonkalsrud EW, Debas HT. Trophic effect of amniotic fluid on fetal gastrointestinal development. J Surg Res 1986;40:291–6.

    Article  CAS  PubMed  Google Scholar 

  8. Pitkin R, Reynolds WA. Fetal ingestion and metabolism of amniotic fluid protein. Am J Obstet Gynecol 1975;123:356–65.

    Article  CAS  PubMed  Google Scholar 

  9. Wesson DE, Muraji T, Kent G, Filler RM, Almalchi T. The effect of intrauterine esophageal ligation on growth of fetal rabbits. J Pediatr Surg 1984;19(4):398–9.

    Article  CAS  PubMed  Google Scholar 

  10. Mclain C. Amniography studies of the gastrointestinal motility of the human fetus. Am J Obstet Gynecol 1963;86:1079–87.

    Article  PubMed  Google Scholar 

  11. Pritchard JA. Deglutition of normal and anencephalic fetuses. Obstet Gynecol 1965;25:289–97.

    CAS  PubMed  Google Scholar 

  12. Abramovich DR, Garden A, Jandial L, Page KR. Fetal swallowing and voiding in relation to hydramnios. Obstet Gynecol 1979;54:15–20.

    Article  CAS  PubMed  Google Scholar 

  13. Bradley RM, Mistretta CM. Swallowing in fetal sheep. Science 1973;179(77):1016–7.

    Article  CAS  PubMed  Google Scholar 

  14. Tomoda S, Brace RA, Longo LD. Amniotic fluid volume and fetal swallowing rate in sheep. Am J Physiol (Regulatory Integrative Comp Physiol) 1985;18:R133-8.

  15. Harding R, SiggerJN, Poore ER, Johnson P. Ingestion in fetal sheep and its relation to sleep states and breathing movements. Q J Exp Physiol 1984;69:477–86.

    Article  CAS  PubMed  Google Scholar 

  16. Brace RA. Fetal blood volume, urine flow, swallowing, and amniotic fluid volume responses to long-term intravascular infusions of saline. Am J Obstet Gynecol 1989;161:1049–54.

    Article  CAS  PubMed  Google Scholar 

  17. Sherman DJ, Ross MG, Day L, Ervin MG. Fetal swallowing: Correlation of electromyography and esophageal fluid flow. Am J Physiol (Regulatory Integrative Comp Physiol 27) 1990;258:R1386–94.

    Article  CAS  Google Scholar 

  18. Szeto HH. Behavioral states and their ontogeny: Animal studies. Semin Perinatol 1992;16:211–6.

    CAS  PubMed  Google Scholar 

  19. Szeto HH, Vo TDH, Dwyer AB, Dogramajian ME, Cox MJ, Senger G. The ontogeny of fetal lamb electrocortical activity: A power spectral analysis. Am J Obstet Gynecol 1985;153:462–6.

    Article  CAS  PubMed  Google Scholar 

  20. Nijland MJ, Day L, Ross MG. Ovine fetal swallowing: Expression of preterm neurobehavioral rhythms. J Matern Fetal Med 2001;10(4):251–7.

    Article  CAS  PubMed  Google Scholar 

  21. Ross MG, Sherman DJ, Ervin MG, Day L, Humme J. Fetal swallowing: Response to systemic hypotension. Am J Physiol (Regulatory Integrative Comp Physiol 26) 1989;257:R130-4.

  22. Sherman DJ, Ross MG, Day L, Humme J, Ervin MG. Fetal swallowing: Response to graded hypoxemia. J Appl Physiol 1991;71:1856–61.

    Article  CAS  PubMed  Google Scholar 

  23. Nijland MJ, Kullama LK, Ross MG. Maternal plasma hypoosmolality: Effects on spontaneous and stimulated ovine fetal swallowing. J Matern Fetal Med 1998;7(4):165–71.

    CAS  PubMed  Google Scholar 

  24. Wirth JB, Epstein AN. Ontogeny of thirst in the infant rat. Am J Physiol 1976;230:188–98.

    Article  CAS  PubMed  Google Scholar 

  25. Bell RJ, Congiu M, Hardy KJ, Wintour EM. Gestation-dependent aspects of the response of the ovine fetus to the osmotic stress induced by maternal water deprivation. Q J Exp Physiol 1984;69(1):187–95.

    Article  CAS  PubMed  Google Scholar 

  26. Powers DR, Brace KA. Fetal cardiovascular and fluid responses to maternal volume loading with lactated Ringer’s or hypotonic solution. Am J Obstet Gynecol 1991;165(5 Pt 1):1504–15.

    Article  CAS  PubMed  Google Scholar 

  27. Ross MG, Sherman DJ, Ervin MG, Day L, Humme J. Stimuli for fetal swallowing: Systemic factors. Am J Obstet Gynecol 1989;161:1559–65.

    Article  CAS  PubMed  Google Scholar 

  28. Ross MG, Kullama LK, Ogundipe OA, Chan K, Ervin MG. Ovine fetal swallowing response to intracerebroventricular hypertonic saline. J Appl Physiol 1995;78:2267–71.

    Article  CAS  PubMed  Google Scholar 

  29. Ross MG, Kullama LK, Ogundipe OA, Chan K, Ervin MG. Central angiotensin II stimulation of ovine fetal swallowing. J Appl Physiol 1994;76:1340–5.

    Article  CAS  PubMed  Google Scholar 

  30. Ross MG, Agnew CL, Fujino Y, Ervin MG, Day L. Concentration thresholds for fetal swallowing and vasopressin secretion. Am J Physiol (Regulatory Integrative Comp Physiol 31) 1992;262:R1057–63.

    Article  CAS  Google Scholar 

  31. Kullama LK, Nijland JM, Ross MG. Development of concentration thresholds for fetal swallowing and AVP stimulation in the preterm ovine fetus. J Matern Fetal Med 1996;5:51–7.

    CAS  PubMed  Google Scholar 

  32. Wood R, Rolls E, Rolls B. Physiological mechanisms for thirst in the nonhuman primate. Am J Physiol (Regulatory Integrative Comp Physiol 11) 1982;242:R423–8.

    Article  CAS  Google Scholar 

  33. Xu Z, Nijland MJ, Ross MG. Plasma osmolality dipsogenic thresholds and c-fos expression in the near-term ovine fetus. Pediatr Res 2001;49(5):678–85.

    Article  CAS  PubMed  Google Scholar 

  34. Xu Z, Ross MG. Appearance of central dipsogenic mechanisms induced by dehydration in near-term rat fetus. Brain Res Dev Brain Res 2000;121(1):11–8.

    Article  CAS  PubMed  Google Scholar 

  35. Blair-West JR, Carey KD, Denton DA, Weisinger RS, Shade RE. Evidence that brain angiotensin II is involved in both thirst and sodium appetite in baboons. Am J Physiol 1998;275(5 Pt 2):R1639–46.

    CAS  PubMed  Google Scholar 

  36. Xu Z, Herbert J. Effects of intracerebroventricular dizocipline (MK801) on dehydration-induced dipsogenic responses, plasma vasopressin and c-fos expression in the rat forebrain. Brain Res 1998;784(1–2):91–9.

    Article  CAS  PubMed  Google Scholar 

  37. Zhu B, Herbert J. Angiotensin II interacts with nitric oxidecyclic GMP pathway in central control of drinking behavior: Mapping with c-fos and NADPH-diaphorase. Neuroscience 1997;79:543–53.

    Article  CAS  PubMed  Google Scholar 

  38. El-Haddad MA, Chao CR, Ma SX, Ross MG. Nitric oxide modulates angiotensin II-induced drinking behavior in the near term ovine fetus. Am J Obstet Gynecol 2000;182(3):713–9.

    Article  CAS  PubMed  Google Scholar 

  39. El-Haddad MA, Chao R, Ma SX, Ross MG. Nitric oxide modulates spontaneous swallowing behavior in near term ovine fetus. Am J Physiol (Regulatory Integrative Comp Physiol) 1999;46:R981-6.

  40. El-Haddad MA, Chao R, Ma SX, Ross MG. Neuronal nitric oxide modulates spontaneous and angiotensin II stimulated fetal swallowing behavior in the near term ovine fetus. Am J Physiol (Regul Integr Comp Physiol) 2002;282(5):R1521-7.

    Google Scholar 

  41. El-Haddad MA, Chao CR, Abdel Sayed A, El-Haddad H, Ross MG. Effects of central angiotensin-II (ang II) receptor antagonism on fetal swallowing and cardiovascular activity. Am J Obstet Gynecol 2001;185(4):828–33.

    Article  CAS  PubMed  Google Scholar 

  42. Nicolaidis S, Galaverna O, Metzler CH. Extracellular dehydration during pregnancy increases salt appetite of offspring. Am J Physiol 1990;258(1 Pt 2):R281–3.

    CAS  PubMed  Google Scholar 

  43. Arguelles J, Lopez-Sela P, Brime JI, Costales M, Vijande M. Changes of blood pressure responsiveness in rats exposed in utero and perinatally to a high-salt environment. Regul Peptides 1996;66(1–2):113–5.

    Article  CAS  Google Scholar 

  44. Crystal SR, Bernstein IL. Infant salt preference and mother’s morning sickness. Appetite 1998;30(3):297–307.

    Article  CAS  PubMed  Google Scholar 

  45. Desai M, Guerra C, Wang S, Ross MG. Programming of hypertonicity in neonatal lambs: resetting of the threshold for vasopressin secretion. Endocrinology 2003;144:4332–7.

    Article  CAS  PubMed  Google Scholar 

  46. Bradley RM, Mistretta CM. Developmental changes in neurophysiological taste responses from the medulla in sheep. Brain Res 1980;191(1):21–34.

    Article  CAS  PubMed  Google Scholar 

  47. Ganchrow JR, Steiner JE, Canetto S. Behavioral displays to gustatory stimuli in newborn rat pups. Dev Psychobiol 1986;19(3):163–74.

    Article  CAS  PubMed  Google Scholar 

  48. Bergamasco NH, Beraldo KE. Facial expressions of neonate infants in response to gustatory stimuli. Braz J Med Biol Res 1990;23(3–4):245–9.

    CAS  PubMed  Google Scholar 

  49. Robinson SR, Wong CH, Robertson SS, Nathanielsz PW, Smotherman WP. Behavioral responses of the chronically in-strumented sheep fetus to chemosensory stimuli presented in utero. Behav Neurosci 1995;109(3):551–62.

    Article  CAS  PubMed  Google Scholar 

  50. El-Haddad MA, Guerra C, Day L, Ross MG. Stimulation of near term ovine fetal swallowing with oral sucrose. Am J Obstet Gynecol 2002;187(4):898–901.

    Article  PubMed  Google Scholar 

  51. Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr Rev 1999;20(1):68–100.

    CAS  PubMed  Google Scholar 

  52. Larsen PJ, Tang-Christensen M, Stidsen CE, Madsen K, Smith MS, Cameron JL. Activation of central neuropeptide Y Yl receptors potently stimulates food intake in male rhesus monkeys. J Clin Endocrinol Metab 1999;84:3781–91.

    CAS  PubMed  Google Scholar 

  53. Leibowitz SF. Brain neuropeptide Y: An integrator of endocrine, metabolic and behavioral processes. Brain Res Bull 1991;27(3–4):333–7.

    Article  CAS  PubMed  Google Scholar 

  54. Saper C, Chou T, Elmquist J. The need to feed. Homeostatic and hedonic control of eating. Neuron 2002;36:199.

  55. Broberger C, Johansen J, Johansson C, Schalling M, Hokfelt T. The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. Proc Natl Acad Sci U S A 1998;95:15043–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Broberger C, Visser TJ, Hokfelt T. Neuropeptide Y innervation and neuropeptide-Y-Y1-receptor-expressing neurons in the paraventricular hypothalamic nucleus of the mouse. Neuroen-docrmology 1999;70:295–305.

    Article  CAS  Google Scholar 

  57. de Quidt ME, Emson PC. Distribution of neuropeptide Y-like immunoreactivity in the rat central nervous system-II. Immu-nohistochemical analysis. Neuroscience 1986;18:545–618.

    Google Scholar 

  58. Hu Y, Bloomquist BT, Cornfield LJ, et al. Identification of a novel hypothalamic neuropeptide Y receptor associated with feeding behavior. J Biol Chem 1996;271(42):26315–9.

    Article  CAS  PubMed  Google Scholar 

  59. Pralong FP, Gonzales C, Voirol MJ, et al. The neuropeptide Y Y1 receptor regulates leptin-mediated control of energy homeostasis and reproductive functions. FASEB J 2002;16(7):712–4.

    Article  CAS  PubMed  Google Scholar 

  60. Sawchenko PE. Toward a new neurobiology of energy balance, appetite, and obesity: The anatomists weigh in. J Comp Neurol 1998;402:435–41.

    Article  CAS  PubMed  Google Scholar 

  61. Watts AG. Understanding the neural control of ingestive be-haviors: Helping to separate cause from effect with dehydration-associated anorexia. Horm Behav 2000;37:261–83.

    Article  CAS  PubMed  Google Scholar 

  62. Grove KL, Chen P, Koegler FH, Schiffmaker A, Smith MS, Cameron JL. Fasting activates neuropeptide Y neurons in the arcuate nucleus and the paraventricular nucleus in the rhesus macaque. Brain Res Mol Brain Res 2003;113:133–8.

    Article  CAS  PubMed  Google Scholar 

  63. Singer LK, Kuper J, Brogan RS, Smith MS, Grove KL. Novel expression of hypothalamic neuropeptide Y during postnatal development in the rat. NeuroReport 2000;11:1075–80.

    Article  CAS  PubMed  Google Scholar 

  64. Sutton SW, Mitsugi N, Plotsky PM, Sarkar DK. Neuropeptide Y (NPY): A possible role in the initiation of puberty. Endocrinology 1988;123:2152–4.

    Article  CAS  PubMed  Google Scholar 

  65. Bradley KL, Cleveland KA, Cheatham B. The adipocyte as a secretory organ: Mechanisms of vesicle transport and secretory pathways. Recent Prog Horm Res 2001;56:329–58.

    Article  CAS  PubMed  Google Scholar 

  66. Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature 2000;404:661–71.

    Article  CAS  PubMed  Google Scholar 

  67. Flier JS, Maratos-Flier E. Obesity and the hypothalamus: Novel peptides for new pathways. Cell 1998;92:437–40.

    Article  CAS  PubMed  Google Scholar 

  68. Dyer CJ, Simmons JM, Matteri RL, Keisler DH. Leptin receptor mRNA is expressed in ewe anterior pituitary and adipose tissues and is differentially expressed in hypothalamic regions of well-fed and feed-restricted ewes. Domest Anim Endocrinol 1997;14(2):119–28.

    Article  CAS  PubMed  Google Scholar 

  69. Henry BA, Goding JW, Alexander WS, et al. Central administration of leptin to ovariectomized ewes inhibits food intake without affecting the secretion of hormones from the pituitary gland: Evidence for a dissociation of effects on appetite and neuroendocrine function. Endocrinology 1999; 140(3): 1175–82.

    Article  CAS  PubMed  Google Scholar 

  70. Yuen BS, McMillen IC, Symonds ME, Owens PC. Abundance of leptin mRNA in fetal adipose tissue is related to fetal body weight. J Endocrinol 1999;163:R1–4.

    Article  PubMed  Google Scholar 

  71. Thomas L, Wallace JM, Aitken RP, Mercer JG, Trayhurn P, Hoggard N. Circulating leptin during ovine pregnancy in relation to maternal nutrition, body composition and pregnancy outcome. J Endocrinol 2001;169:465–76.

    Article  CAS  PubMed  Google Scholar 

  72. Yuen BS, Owens PC, McFarlane JR, et al. Circulating leptin concentrations are positively related to leptin messenger RNA expression in the adipose tissue of fetal sheep in the pregnant ewe fed at or below maintenance energy requirements during late gestation. Biol Reprod 2002;67(3):911–6.

    Article  CAS  PubMed  Google Scholar 

  73. Jaquet D, Leger J, Levy-Marchal C, Oury JF, Czernichow P. Ontogeny of leptin in human fetuses and newborns: Effect of intrauterine growth retardation on serum leptin concentrations. J Clin Endocrinol Metab 1998;83:1243–6.

    Article  CAS  PubMed  Google Scholar 

  74. Schubring C, Keiss W, Englaro P, et al. Levels of leptin in maternal serum, amniotic fluid, and arterial and venous cord blood: Relation to neonatal and placental weight. J Clin Endo-crinol Metab 1997;82:1480–3.

    Article  CAS  Google Scholar 

  75. Forhead AJ, Thomas L, Crabtree J, et al. Plasma leptin concentration in fetal sheep during late gestation: Ontogeny and effect of glucocorticoids. Endocrinology 2002;143(4):1166–73.

    Article  CAS  PubMed  Google Scholar 

  76. Legradi G, Emerson CH, Ahima RS, Flier JS, Lechan RM. Leptin prevents fasting-induced suppression of prothyrotropin-releasing hormone messenger ribonucleic acid in neurons of the hypothalamic paraventricular nucleus. Endocrinology 1997;138:2569–76.

    Article  CAS  PubMed  Google Scholar 

  77. Ahima RS, Bjorbaek C, Osei S, Flier JS. Regulation of neuronal and glial proteins by leptin: Implications for brain development. Endocrinology 1999;140:2755–62.

    Article  CAS  PubMed  Google Scholar 

  78. Ahima RS, Hileman SM. Postnatal regulation of hypothalamic neuropeptide expression by leptin: Implications for energy balance and body weight regulation. Regul Pept 2000;92:1–7.

    Article  CAS  PubMed  Google Scholar 

  79. Mistry AM, Swick A, Romsos DR. Leptin alters metabolic rates before acquisition of its anorectic effect in developing neonatal mice. Am J Physiol 1999;277:R742-7.

  80. Cowley MA, Smart JL, Rubinstein M, et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 2001;411:480–4.

    Article  CAS  PubMed  Google Scholar 

  81. Tang-Christensen M, Hoist JJ, Hartmann B, Vrang N. The arcuate nucleus is pivotal in mediating the anorectic effects of centrally administered leptin. NeuroReport 1999;10:1183–7.

    Article  CAS  PubMed  Google Scholar 

  82. Roberts TJ, Caston-Balderrama A, Nijland MJ, Ross MG. Central neuropeptide Y stimulates ingestive behavior and increases urine output in the ovine fetus. Am J Physiol Endocrinol Metab 2000;279(3):E494–500.

    Article  CAS  PubMed  Google Scholar 

  83. El-Haddad MA, Ismail Y, Guerra C, Day L, Ross MG. Neuropeptide Y administered into cerebral ventricles stimulates sucrose ingestion in the nearterm ovine fetus. Am J Obstet Gynecol 2003;189:949–52.

    Article  CAS  PubMed  Google Scholar 

  84. Roberts TJ, Nijland MJ, Caston-Balderrama A, Ross MG. Central leptin stimulates ingestive behavior and urine flow in the near term ovine fetus. Horm Metab Res 2001;33(3):144–50.

    Article  CAS  PubMed  Google Scholar 

  85. Desai M, Hales CN. Role of fetal and infant growth in programming metabolism in later life. Biol Rev Camb Philos 1997;72:329–48.

    Article  CAS  Google Scholar 

  86. Barker DJ. Maternal and fetal origins of coronary heart disease. J R Coll Physicians Lond 1994;28:544–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Jackson SC, Langley-Evans, McCarthy HD. Nutritional influences in early life upon obesity and body proportions. Ciba Found Symp 1996;201:118–29.

    CAS  PubMed  Google Scholar 

  88. Langley-Evans DS, Gardner DS, Jackson AA. Association of disproportionate growth of fetal rats in late gestation with raised systolic blood pressure in later life. J Reprod Fertil 1996;106:307–12.

    Article  CAS  PubMed  Google Scholar 

  89. Gallaher BW, Breier BH, Keven CL, Harding JE. Fetal programming of insulin-like growth factor (IGF)-I and IGF-binding protein-3: Evidence for an altered response to undernutrition in late gestation following exposure to pericon-ceptual undernutrition in the sheep. J Endocrinol 1998;159:501–8.

    Article  CAS  PubMed  Google Scholar 

  90. Warnes KE, Morris MJ, Symonds ME, et al. Effects of increasing gestation, Cortisol and maternal undernutrition on hypothalamic neuropeptide Y expression in the sheep fetus. J Neuroendocrinol 1998;10:51–7.

    Article  CAS  PubMed  Google Scholar 

  91. Buchbinder A, Lang U, Baker RS, Khoury JC, Mershon J, Clark KE. Leptin in the ovine fetus correlates with fetal and placental size. AmJ Obstet Gynecol 2001;185(4):786–91.

    Article  CAS  Google Scholar 

  92. Jones AP, Simson EL, Friedman MI. Gestational undernutrition and the development of obesity in rats. J Nutr 1984;114:1484–92.

    CAS  PubMed  Google Scholar 

  93. Vickers MH, Breier BH, Cutfield WS, Hofman PL, Gluckman PD. Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition. Am J Physiol Endocrinol Metab 2000;279:E83–7.

    Article  CAS  PubMed  Google Scholar 

  94. Seufert J. The significance of leptin for the pathogenesis of diabetes mellitus type 2. Direct effects on endocrine pancreas. Internist (Berl) 1999;40(8):894–7.

    Article  CAS  Google Scholar 

  95. Faust IM, Johnson PR, Hirsch J. Long-term effects of early nutritional experience on the development of obesity in rats. J Nutr 1980;110:2027–34.

    Article  CAS  PubMed  Google Scholar 

  96. Plagemann A, Harder T, Rake A, et al. Perinatal elevation of hypothalamic insulin, acquired malformation of hypothalamic galaninergic neurons, and syndrome X-like alterations in adult-hood of neonatally overfed rats. Brain Res 1999;836:146–55.

    Article  CAS  PubMed  Google Scholar 

  97. Plagemann A, Harder T, Rake A, et al. Observations on the orexigenic hypothalamic neuropeptide Y-system in neonatally overfed weanling rats. J Neuroendocrinol 1999;11:541–6.

    Article  CAS  PubMed  Google Scholar 

  98. Davidowa H, Plagemann A. Different responses of ventromedial hypothalamic neurons to leptin in normal and early postnatally overfed rats. Neurosci Lett 2000;293:21–4.

    Article  CAS  PubMed  Google Scholar 

  99. Davidowa H, Plagemann A. Decreased inhibition by leptin of hypothalamic arcuate neurons in neonatally overfed rats. Neuroreport 2000;11:2795–8.

    Article  CAS  PubMed  Google Scholar 

  100. Davidowa H, Plagemann A. Inhibition by insulin of hypothalamic VMN neurons in rats overweight due to postnatal over-feeding. Neuroreport 2001;12:3201–4.

    Article  CAS  PubMed  Google Scholar 

  101. Davidowa H, Li Y, Plagemann A. Altered responses to orexigenic (ARP, MCH) and anorexigenic (ct-MSH, CART) neuropeptides of paraventricular hypothalamic neurons in early postnatally overfed rats. Eur J Neurosci 2003;18(3):613–21.

    Article  PubMed  Google Scholar 

  102. Goland RS, Jozak S, Warren WB, Conwell IM, Stark RI, Tropper PJ. Elevated levels of umbilical cord plasma corticotropin-releasing hormone in growth-retarded fetuses. J Clin Endocrinol Metab 1993;77:1174–9.

    CAS  PubMed  Google Scholar 

  103. Soh EB, Mitchell MD, Keelan J A. Does leptin exhibit cytokinelike properties in tissues of pregnancy? Am J Reprod Immunol 2000;43:292–8.

    Article  CAS  PubMed  Google Scholar 

  104. Kronfeld-Schor N, Zhao J, Silvia BA, et al. Steroid-dependent up-regulation of adipose leptin secretion in vitro during pregnancy in mice. Biol Reprod 2000;63:274–80.

    Article  CAS  PubMed  Google Scholar 

  105. Levin BE. The obesity epidemic: Metabolic imprinting of genetically susceptible neural circuits. Obesity Res 2000;8:342–7.

    Article  CAS  Google Scholar 

  106. Dorner G. Hormone-dependent brain development and neuroendocrine prophylaxis. Exp Clin Endocrinol 1989;94:4–22.

    Article  CAS  PubMed  Google Scholar 

  107. Plagemann A, Heidrich I, Gotz F, Rohde W, Dorner G. Obesity and enhanced diabetes and cardiovascular risk in adult rats due to early postnatal overfeeding. Exp Clin Endocrinol 1992;99:154–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Perinatal Research Laboratories, Harbor/UCLA Medical Center, UCLA School of Medicine, Los Angeles, California, USA

    M. A. El-Haddad MD, M. Desai PhD, D. Gayle PhD & M. G. Ross MD, MPH

Authors
  1. M. A. El-Haddad MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Desai PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Gayle PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. G. Ross MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. A. El-Haddad MD.

Additional information

Supported by grants ROl DK43311 and R03 HD39671-01 (MGR) and K08 010187-01-00 (MAE) from the National Institutes of Health.

Rights and permissions

Reprints and permissions

About this article

Cite this article

El-Haddad, M.A., Desai, M., Gayle, D. et al. In Utero Development of Fetal Thirst and Appetite: Potential for Programming. Reprod. Sci. 11, 123–130 (2004). https://doi.org/10.1016/j.jsgi.2003.12.001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.jsgi.2003.12.001

Key words

Search

Navigation