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Topical Reviews |
1 Rowett Research Institute, Bucksburn, Aberdeen AB21 9SB, UK
2 University of Colorado, Health Sciences Center, Perinatal Research Center, Aurora, CO 80010, USA
Intrauterine growth restriction (IUGR) still accounts for a large incidence of infant mortality and morbity worldwide. Many of the circulatory and transport properties of the sheep placenta are similar to those of the human placenta and as such, the pregnant sheep offers an excellent model in which to study the development of IUGR. Two natural models of ovine IUGR are those of hyperthermic exposure during pregnancy, and adolescent overfeeding, also during pregnancy. Both models yield significantly reduced placental weights and an asymmetrically growth-restricted fetus, and display altered maternal hormone concentrations, indicative of an impaired trophoblast capacity. Additionally, impaired placental angiogenesis and uteroplacental blood flow appears to be an early defect in both the hyperthermic and adolescent paradigms. The effects of these alterations in placental functional development appear to be irreversible. IUGR fetuses are both hypoxic and hypoglycaemic, and have reduced insulin and insulin-like growth factor-1 (IGF-1), and elevated concentrations of lactate. However, fetal utilization of oxygen and glucose, on a weight basis, remain constant compared with control pregnancies. Maintained utilization of these substrates, in a substrate-deficient environment, suggests increased sensitivities to metabolic signals, which may play a role in the development of metabolic diseases in later adult life.
(Received 22 December 2004;
accepted after revision 14 March 2005;
first published online 17 March 2005)
Corresponding author J. M. Wallace: Rowett Research Institute, Bucksburn, Aberdeen AB21 9SB, UK. Email: jacqueline.wallace{at}rri.sari.ac.uk
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