EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR-I AND FACTOR-II IN CONCEPTUSES FROM NORMAL AND DIABETIC MICE

Insulin-like growth factors (IGF-I and IGF-II) play an important regulatory role in fetal growth and development. Alterations in expression of these growth factors may result in developmental abnormalities, macrosomia, and intrauterine growth retardation, which occur with a higher incidence in diabetic pregnancies. In situ hybridization histochemistry was employed to investigate the distribution and abundance of IGF-I and IGF-II in peri-implantation and postimplantation conceptuses from normal and streptozotocin-treated diabetic mice. Animals were sacrificed on gestational days 5, 6, 7, 8, and 9. The entire uterine horn was prepared for hybridization with antisense and sense alpha-S-35-dATP labeled oligonucleotide probes for IGF-I, IGF-II, and mouse beta-actin. IGF-I transcript was apparent only in myometrium at 6 days of gestation in normal and diabetic mice. IGF-II transcripts were restricted to trophoectoderm cells within the implantation chamber on day 5. Following implantation, IGF-II transcripts were found in trophoectodermal derivatives, primitive endoderm, mesoderm, heart, walls of the foregut, and mesenchyme in normal and diabetic postimplantation conceptuses. There were no apparent differences between normal and diabetic samples in the distribution and abundance of the IGF-II transcript from gestational days 7, 8, and 9. The embryos from the diabetic mother at day 6 were growth retarded and had a significant decrease in the expression of IGF-II. These results suggest that maternal hyperglycemia may retard development of the early implanting conceptus in a narrow window around day 6 through a mechanism involving decreased IGF-II expression. Fetuses from diabetic pregnancies that escape this critical period appear to develop and express IGF-II in an equivalent manner to those of the control group. (C) 1994 Wiley-Liss, Inc.