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INTEGRATIVE |
1 Perinatal Center, Institute of Neuroscience and Physiology, Göteborg University, Sweden
2
University of Florida College of Medicine, Gainesville, FL, USA
3
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA, USA
4
Department of Obstetrics and Gynecology, University of Cincinnati, Cincinnati, OH, USA
Intrauterine growth restriction (IUGR) represents an important risk factor for perinatal complications and for adult disease. IUGR is associated with a down-regulation of placental amino acid transporters; however, whether these changes are primary events directly contributing to IUGR or a secondary consequence is unknown. We investigated the time course of changes in placental and fetal growth, placental nutrient transport in vivo and the expression of placental nutrient transporters in pregnant rats subjected to protein malnutrition, a model for IUGR. Pregnant rats were given either a low protein (LP) diet (n = 64) or an isocaloric control diet (n = 66) throughout pregnancy. Maternal insulin, leptin and IGF-I levels decreased, whereas maternal amino acid concentrations increased moderately in response to the LP diet. Fetal and placental weights in the LP group were unaltered compared to control diet at gestational day (GD) 15, 18 and 19 but significantly reduced at GD 21. Placental system A transport activity was reduced at GD 19 and 21 in response to a low protein diet. Placental protein expression of SNAT2 was decreased at GD 21. In conclusion, placental amino acid transport is down-regulated prior to the development of IUGR, suggesting that these placental transport changes are a cause, rather than a consequence, of IUGR. Reduced maternal levels of insulin, leptin and IGF-1 may link maternal protein malnutrition to reduced fetal growth by down-regulation of key placental amino acid transporters.
(Received 5 July 2006;
accepted after revision 14 August 2006;
first published online 17 August 2006)
Corresponding author N. Jansson: Perinatal Center, Institute of Neuroscience and Physiology, Department of Physiology, Göteborg University, P.O Box 432, 405 30 Göteborg, Sweden. Email: nina.jansson{at}fysiologi.gu.se
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