Ontogeny of insulin-like growth factor 1 in a rabbit model of growth retardation

Many cases of intrauterine growth retardation (IUGR) result from placental insufficiency, but the molecular signals accompanying this event are unknow n. Insulin-like growth factor 1 (IGF-1) is a potent mitogen for fetal tissu es and is lowered in the serum of human infants with IUGR. The rabbit provi des an optimal model for the study of IUGR based on fetal position. To dete rmine if IGF-1 expression is altered in the growth-retarded fetus, this nat urally occurring rabbit model of IUGR was used. Four fetal rabbit pairs wer e harvested on Days 21, 23, 25, 27, 29, and 31 of their normal 31-day gesta tion; they were identified based on uterine position as normal or growth re tarded. Fetal weight was recorded and the serum, amniotic fluid, liver, kid ney, and small intestine (SI) were collected. The SI was divided into three equal segments: proximal, middle, and distal. Reverse transcription polyme rase chain reaction (RT-PCR) was used to measure IGF-1/beta-actin mRNA dens itometric band ratios in all tissues. Radioimmunoassay (RIA) was used to me asure IGF-1 protein levels in the serum and amniotic fluid. Statistical ana lysis was performed using ANOVA and the paired Student's t test. Weights we re decreased in fetuses with IUGR at all time points (P < 0.05), further va lidating this rabbit model in the study of IUGR. Liver, proximal, and dista l SI IGF-1 mRNA decreased during late gestation (P < 0.01). Kidney IGF-1 mR NA increased throughout late gestation (P < 0.01). Compared with their norm al counterparts, fetuses with IUGR had a trend toward decreased IGF-1 mRNA in the kidney, liver, and SI at all time points, reaching significance in t he liver on Day 27 (P = 0.002). Serum IGF-1 decreased throughout gestation in all fetuses < 0.05). Compared with normal fetuses, fetuses with IUGR had lower serum IGF-1 at all time points, reaching significance at Day 27 (P = 0.02). Amniotic fluid IGF-1 was lower in fetuses with IUGR than in normal fetuses, though not quite reaching significance. Compared with normal fetus es, growth-retarded fetal rabbits trend toward depressed liver, kidney, and intestinal expression of IGF-1 mRNA and lower serum and amniotic fluid IGF -1 protein. Serum IGF-1 levels correlate with fetal weight change. Further studies and potential manipulation of fetal IGF-1 are warranted to investig ate potential prenatal intervention in the treatment of IUGR. (C) 2000 Acad emic Press.