It has been demonstrated in several animal models that undernutrition in utero has significant long lasting effects on subsequent fetal and postnatal development. To address the hypothesis that the insulin-like growth factors (IGFs) may mediate such effects, our study examined whether a period of periconceptual maternal undernutrition could have a lasting influence on the IGF axis in the fetal sheep. Ewes were either allowed to feed ad libitum or kept undernourished from day 60 prior to mating until day 30 after conception, and then both groups were allowed to feed ad libitum. These groups were further divided at day 105 of gestation, either being fed ad libitum or undernourished until day 115 of gestation. Fetal and maternal blood samples were obtained at both day 105 and 115 of gestation. We describe the development of a specific homologous RIA to measure ovine IGF-binding protein-3 (IGFBP-3) in fetal and maternal sheep plasma. Fetal plasma IGFBP-3 and IGF-I concentrations were significantly (P<0.05) reduced at day 115 of gestation after maternal undernutrition. The fetal plasma IGFBP-2 levels were unchanged. The degree of reduction in fetal plasma IGFBP-3 and IGF-I between day 105 and 115 of gestation as a response to acute maternal undernutrition was significantly greater (P<0.05) in fetuses of mothers receiving low periconceptual nutrition. The response of maternal plasma IGFBP-3 and IGF-I to undernutrition did not depend on the level of periconceptual nutrition. Western blot data indicate that changes in either maternal or fetal plasma IGFBP-3 concentrations were not the result of increased proteolytic activity. These results suggest that exposure to maternal periconceptual undernutrition reprograms IGFBP-3 and IGF-I regulation in the developing sheep fetus, altering its response to undernutrition in late gestation.

This article has been cited by other articles:

				T. P. Fleming, W. Y. Kwong, R. Porter, E. Ursell, I. Fesenko, A. Wilkins, D. J. Miller, A. J. Watkins, and J. J. Eckert The Embryo and Its Future Biol Reprod, October 1, 2004; 71(4): 1046 - 1054. [Abstract] [Full Text] [PDF]

				M. A. El-Haddad, M. Desai, D. Gayle, and M. G. Ross In Utero Development of Fetal Thirst and Appetite: Potential for Programming Reproductive Sciences, April 1, 2004; 11(3): 123 - 130. [Abstract] [PDF]

				S. R. Ravelich, B. H. Breier, S. Reddy, J. A. Keelan, D. N. Wells, A. J. Peterson, and R. S.F. Lee Insulin-Like Growth Factor-I and Binding Proteins 1, 2, and 3 in Bovine Nuclear Transfer Pregnancies Biol Reprod, February 1, 2004; 70(2): 430 - 438. [Abstract] [Full Text] [PDF]

				P. D. Gluckman and C. S. Pinal Regulation of Fetal Growth by the Somatotrophic Axis J. Nutr., May 1, 2003; 133(5): 1741S - 1746. [Abstract] [Full Text] [PDF]

				K. Moritz, A. Butkus, V. Hantzis, A. Peers, E. M. Wintour, and M. Dodic Prolonged Low-Dose Dexamethasone, in Early Gestation, Has No Long-Term Deleterious Effect on Normal Ovine Fetuses Endocrinology, April 1, 2002; 143(4): 1159 - 1165. [Abstract] [Full Text] [PDF]

				R. Bajoria, M. J. Gibson, S. Ward, S. R. Sooranna, J. P. Neilson, and M. Westwood Placental Regulation of Insulin-Like Growth Factor Axis in Monochorionic Twins with Chronic Twin-Twin Transfusion Syndrome J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3150 - 3156. [Abstract] [Full Text] [PDF]

				L. R. Green Programming of Endocrine Mechanisms of Cardiovascular Control and Growth Reproductive Sciences, April 1, 2001; 8(2): 57 - 68. [Abstract] [PDF]

				W. Kwong, A. Wild, P Roberts, A. Willis, and T. Fleming Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension Development, January 10, 2000; 127(19): 4195 - 4202. [Abstract] [PDF]