Delayed Disaccharidase Development in a Rabbit Model of Intrauterine Growth Retardation

Abstract

Intrauterine growth retardation (IUGR) affects almost 10% of infants born in the United States. It may be responsible for delayed gastrointestinal function and is an important cause of perinatal morbidity and mortality. The New Zealand White rabbit provides an optimal model for the study of naturally occurring IUGR. At term, birth weight is determined by fetal position within the bicornuate uterus. The small intestinal disaccharidase enzymes are indicators of bowel maturity and function. To examine potential differences in disaccharidase development between normal and IUGR fetuses, this rabbit model was investigated. Jejunum was harvested at multiple stages in rabbit development including the third trimester fetus, neonate, and adult. Lactase, maltase, and sucrase enzyme activity, as well as total protein content, was determined. Results were analyzed by the 2-tailed t test and ANOVA. Lactase activity appeared in the mid-third trimester, peaked in the early neonatal period, then declined to adult levels. Maltase activity appeared in the early third trimester and gradually rose to adult levels. Sucrase remained at trace levels until the mid-neonatal period, reaching adult levels by weaning. Both lactase and maltase activity were depressed in IUGR fetuses compared with their normal littermates. This pattern of disaccharidase depression continued into the neonatal period until catch-up growth occurred at 2 wk when levels equalized. This report describes differential small intestinal disaccharidase development between normal and growthretarded rabbit fetuses in a naturally occurring model of IUGR. The third trimester is a critical period in the maturation of the fetal gut for the postnatal functions of nutrient propulsion and absorption. The terminal stages of digestion are accomplished by the disaccharide hydrolases, disaccharidases, which are located on the enterocyte brush-border membrane. Disaccharidase activity parallels the digestive needs of the animal and is indicative of intestinal function and maturity. Disaccharidase ontogeny has been described in human (1) and animal models, including fetal and neonatal rabbits (2). Developmental delays in fetal disaccharidase activity have been reported in rat models of surgically created intrauterine growth retardation (IUGR) (3) and fetal rabbit gastroschisis (our unpublished observation).The pregnant New Zealand White rabbit has a bicornuate uterus containing multiple fetuses within individual amniotic cavities ( Fig. 1). By convention, the fetus at the ovarian end is numbered 1. At term, the weight ratio of the growth-retarded fetus (position 3) to the ipsilateral normal fetus (position 1) is consistently 0.85, an example of naturally occurring IUGR (4). We hypothesize that IUGR rabbits are not only small but also have immature gastrointestinal development that impairs postnatal bowel function. To test this hypothesis, we studied the development of small intestinal disaccharidase enzymes. These enzymes are indicators of intestinal maturity and function in both norma...

Intrauterine Growth Restriction Alters Postnatal Colonic Barrier Maturation in Rats

“…This phenomenon could explain the reduction in intestinal development observed at birth in infants with IUGR (20) and some animal models of IUGR (21). IUGR impairs cell proliferation (22) and absorptive (23) and digestive (24) functions in small intestine. It was found to produce alterations in colonic development, such as a reduction in colonic length or weight, or in the number of goblet cells in animal models of IUGR (20,25).…”

Effects of restricted feeding on fetal and placental development in pregnant rabbits

“…Rabbits have been used in various studies as a model animal of naturally occurring intrauterine growth retardation (Buchmiller-Crair et al, 2001, Skarsgard et al, 2001Cellini et al, 2006). However, there are a somewhat small number of reports of a relationship between intrauterine growth retardation and the occurrence of abortion and/or structural changes in the placenta.…”

Intraplacental Gene Therapy with Ad-IGF-1 Corrects Naturally Occurring Rabbit Model of Intrauterine Growth Restriction

“…29,30 The rabbit has a bicornuate uterus, with four to six fetuses in each horn. In both horns, the presence of a uterine vascular watershed area at position 3 from the ovarian end makes the fetus at this position naturally growth restricted (Runt), with a term birth weight ratio of 0.85 relative to other fetuses.…”