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Endocrinology, doi:10.1210/en.2008-1648
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Endocrinology Vol. 150, No. 10 4634-4642
Copyright © 2009 by The Endocrine Society

Effects of Maternal Global Nutrient Restriction on Fetal Baboon Hepatic Insulin-Like Growth Factor System Genes and Gene Products

Cun Li, Natalia E. Schlabritz-Loutsevitch, Gene B. Hubbard, Victor Han, Karen Nygard, Laura A. Cox, Thomas J. McDonald and Peter W. Nathanielsz

Center for Pregnancy and Newborn Research (C.L., N.E.S.-L., T.J.M., P.W.N.), University of Texas Health Sciences Center, San Antonio, Texas 78229; Departments of Comparative Medicine (C.L., N.E.S.-L., G.B.H., T.J.M., P.W.N.) and Genetics (L.A.C.) and Southwest National Primate Research Center (G.B.H.), Southwest Foundation for Biomedical Research, San Antonio, Texas 78227; and Children’s Health Research Institute (V.H., K.N.), The University of Western Ontario, London, Ontario, Canada N6A 5B8

Address all correspondence and requests for reprints to: Cun Li, M.D., Center for Pregnancy and Newborn Research, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MSC 7836, San Antonio, Texas 78229. E-mail: lic{at}uthscsa.edu.

Knowledge of altered maternal nutrition effects on growth-regulating systems is critical to understanding normal and abnormal fetal development. There are many reports of hepatic fetal IGF system responses to maternal nutrient restriction (MNR) during pregnancy in rodents and sheep but none in nonhuman primates. We determined effects of MNR on the fetal baboon hepatic IGF system. Social groups of female baboons were fed ad libitum, controls, or 70% controls (MNR) from 0.16 to 0.5 gestation and fetuses delivered by cesarean section. Fetal liver tissue was analyzed for IGF-I, IGF-II, and IGF binding protein (IGFBP)-3 mRNA by in situ hybridization and quantitative RT-PCR and protein by immunohistochemistry (IHC); IGF-I receptor, IGF-II receptor by quantitative RT-PCR and IHC and IGFBP-1 by in situ hybridization and IHC. MNR did not alter fetal body or liver weight. Fetal hepatic glycogen staining increased with MNR. MNR reduced fetal hepatic IGF-I and IGF-II and increased IGFBP-1 mRNA and decreased IGF-I, IGF-II, IGF-I receptor, and IGF-II receptor protein and increased protein for IGFBP-1 and IGFBP-3. MNR increased caspase-3, indicating apoptosis and decreased Akt staining, indicating decreased nutrient sensing. In conclusion, whereas fetal body and liver weights did not change in response to moderate MNR during the first half of baboon pregnancy, the major indices of function of the hepatic IGF system measured were all reduced.







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