The effect of intermittent umbilical cord occlusion on insulin-like growth factors and their binding proteins in preterm and near-term ovine fetuses.
Intermittent umbilical cord compression with resultant fetal hypoxia can have a negative impact on fetal growth and development. Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are the most important regulators of fetal growth. In preterm (107-108 days of gestation) and near-term (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 animals (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. Ewes were euthanized at the end of day 4, and fetal heart, lung, kidney, liver, skeletal muscle and placenta were collected. During UCOs, PO(2! ) fell (by approximately 13 mmHg), pH fell (by approximately 0.05) and PCO(2) increased (by approximately 7 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 body or organ weight between UCO and control fetuses. No significant changes were observed in plasma IGF-I and -II concentrations or IGFBP-1, -2, -3 or -4 levels throughout the 4-day study at either gestational age. In the preterm group UCO fetuses, IGF-II mRNA (1.2-6.0 kb) levels were lower in fetal lung (33%, P<0.05), heart (54%, P<0.01) and skeletal muscle (29%, P<0.05), but 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 kidney (22%, P<0.01), but hig! her 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-term 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 expression of genes encoding certain peptides of the fetal IGF system in selected tissues in preterm fetuses than that in near-term fetuses. Altered IGFBP-2 mRNA levels with reduced IGF-II mRNA levels in selected tissues may mediate changes in growth and/or differentiation that might become apparent if the length of the UCO study were extended.
Green
L R
LR
MRC Group in Fetal and Neonatal Health and Development, Department of Physiology, The Lawson Research Institute, and The Child Health Research Institute, The University of Western Ontario, London, Ontario N6A 4V2, Canada. LucyRGreen@hotmail.com
Kawagoe
Y
Y
Hill
D J
DJ
Richardson
B S
BS
Han
V K
VK
D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005318:Fetal Heart / Q000737:chemistry; D005311:Fetal Hypoxia / Q000378:metabolism*; D005333:Fetus / Q000737:chemistry / Q000378:metabolism*; D005865:Gestational Age; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood / Q000235:genetics; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood / Q000235:genetics; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000235:genetics; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000097:blood / Q000235:genetics; D018969:Insulin-Like Growth Factor Binding Proteins / Q000032:analysis / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000235:genetics; D007668:Kidney / Q000737:chemistry / Q000196:embryology; D008099:Liver / Q000737:chemistry / Q000196:embryology; D010920:Placenta / Q000737:chemistry; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D012756:Sheep; D013002:Somatomedins / Q000032:analysis / Q000378:metabolism*
D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II