Uteroplacental insufficiency decreases small intestine growth and alters apoptotic homeostasis in term intrauterine growth retarded rats

Human and animal studies demonstrate that uteroplacental insufficiency and subsequent intrauterine growth retardation (IUGR) decrease intestinal growth and lead to both an increased incidence of feeding intolerance and necrotizing enterocolitis. Our objective was to determine the effects of uteroplacental insufficiency upon small intestine growth, histology, gene expression of the apoptosis related proteins Bcl-2, Bax and p53, and caspase-3 activity. For this purpose, we induced uteroplacental insufficiency through bilateral uterine artery ligation on day 19 of gestation in fully anesthetized pregnant Sprague-Dawley rats and harvested pups at term 2 days latter. Pups from sham surgeries served as controls. Uteroplacental insufficiency reduced cell count per crypt and decreased small intestinal weight. In association with these changes, IUGR intestinal Bcl-2 mRNA levels were decreased significantly, and Bax and p53 mRNA were significantly increased in distal ileum. Immunohistochemistry for Bcl-2, Bax, and p53 revealed similar findings. In association with the decreased Bcl-2 and the increased Bax gene expression, increased caspase-3 activity characterized the IUGR distal ileum. We conclude that uteroplacental insufficiency affects intestinal growth and morphology in association with altered gene expression of apoptosis related proteins. We speculate that the morphological change and associated altered apoptotic homeostasis contribute to the increased morbidity of infants affected by uteroplacental insufficiency. (C) 2004 Elsevier Ireland Ltd. All rights reserved.