The effect of intermittent umbilical cord occlusion on insulin-like growthfactors and their binding proteins in preterm and near-term ovine fetuses

Intermittent umbilical cord compression with resultant fetal hypoxia can ha ve a negative impact on fetal growth and development. Insulin-like growth f actors (IGFs) and their binding proteins (IGFBPs) are the most important re gulators of fetal growth. In preterm (107-108 days of gestation) and near-t erm(128-131 days of gestation) ovine fetuses. we have determined the effect of intermittent umbilical cord occlusion (UCO) over a period of 4 days on the profile and expression of IGFs and IGFBPs. In experimental group animal (preterm n=7, near term n = 7) UCOs were carried out by complete inflation of an occluder cuff(duration 90 s) every 30 min for 3-5 h each day, while control fetuses (preterm n=7; near term n=7) received no UCOs. Eu es were e uthanized at the end of day 4, and fetal heart, lung, kidney, liver, skelet al muscle and placenta were collected. During UCOs, PO2 fell roy similar to 13 mmHg), pH fell (by similar to 0.05) and PCO2 increased (by similar to7 mmHg) and changed to a similar extent in both preterm and near-term groups. In both preterm and near-term groups, there was no difference in fetal bod y or organ weight between UCO and control fetuses. No significant changes w ere observed in plasma IGF-I and -II concentrations or IGFDP-1, -2, -3 or - 4 levels throughout the 4-day study at either gestational age. In the prete rm group UCO fetuses. IGF-II mRNA (1.2-6.0 kb) levels were lower in fetal l ung (33%, P<0.05), heart (54%, P<0.01) and skeletal muscle (29%, P<0.05), b ut there were no differences in IGF-I mRNA levels (7.3 kb); IGFBP-2 mRNA (1 .5 kb) levels were lower in the right lobe of the liver (42%, P<0.05) and k idney (22%, P<0.01), but higher in the heart (72%, P<0.01). while IGFBP-4 ( 2.4 kb) levels were lower in skeletal muscle (21%, P<0.01). In the near-ter m group UCO fetuses, IGFBP-2 mRNA levels were greater in the placenta (39%, P<0.05). Thus, intermittent UCO as studied has a greater effect on the exp ression of genes encoding certain peptides of the fetal IGF system in selec ted tissues in preterm fetuses than that in near-term fetuses. Altered IGFB P-2 mRNA levels with reduced IGF-II mRNA levels in selected tissues may med iate changes in growth and/or differentiation that might become apparent if the length of the UCO study were extended.