MATERNAL DIABETES INDUCES UP-REGULATION OF HEPATIC INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-1 MESSENGER-RNA EXPRESSION, GROWTH-RETARDATION AND DEVELOPMENTAL DELAY AT THE SAME STAGE OF RAT FETAL DEVELOPMENT

Since maternal diabetes is associated with fetal growth abnormalities in humans and rats, effects of maternal diabetes on fetal expression o f genes regulating growth are of interest. Increased expression of Ins ulin-like Growth Factor Binding Protein-1 (IGFBP-1) is associated with several examples of growth retardation and is upregulated in response to diabetes. As we have shown previously, IGFBP-1 expression is upreg ulated in gestational day(GD) 14 rat fetuses in response to maternal d iabetes. Here we analyze the effect of streptozotocin-induced maternal diabetes on IGFBP-1 mRNA expression during GD12-16 of rat fetal devel opment, using in situ hybridization. IGFBP-1 mRNA was more abundant in GD12-14 fetal livers from diabetic darns than in livers of age-matche d controls. This upregulation is not due to the approximately 1-day fe tal developmental delay associated with maternal diabetes, as there is no gross difference in the level of IGFBP-1 mRNA in GD13 vs GD12 or G D14 vs GD13 control fetal livers. At GD15-16, however, we detected lit tle difference in IGFBP-1 expression between experimental and control fetuses. This transient period of maternal diabetes-stimulated IGFBP-1 mRNA. expression (GD12-14) is coincident with the sensitive period fo r maternal diabetes-induced defects in fetal growth and development, s uggesting that IGFBP-1 is involved in the regulation of fetal growth a nd development in response to the maternal condition.