LOCALIZATION OF INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-4 EXPRESSION IN THE MOUSE UTERUS DURING THE PERIIMPLANTATION PERIOD

Previous studies have suggested a role for insulin-like growth factors (IGFs) in both embryo and trophoblast growth, as well as in uterine d ifferentiation. Included in the IGF family are the IGF binding protein s (IGFBPs). In the current study we have demonstrated, by Western liga nd blot of mouse uterine tissue extracts, a dramatic increase in IGFBP -4 at the time of embryo implantation. As an extension of this finding , we used in situ hybridization to examine the ontogeny and anatomical localization of IGFBP-4 mRNA in the mouse uterus during the peri-impl antation period. On gestational Day 2, while the embryos are still in the oviduct, no uterine IGFBP-4 mRNA signal was observed. However, on gestational Day 4, when the embryos are free in the uterine lumen, IGF BP-4 mRNA was present in the uterine stroma underlying the luminal epi thelium. By gestational Day 6, approximately 24 h after implantation, a IGFBP-4 mRNA signal was intense at each implantation site and extend ed throughout the decidua. A signal was absent in the uterine tissue b etween implantation sites. By gestational Day 8, the IGFBP-4 mRNA sign al was reduced and confined to the stroma nearest the myometrium. The specific anatomical and temporal nature of the IGFBP-4 mRNA expression suggests a physiologic role for this binding protein in the implantat ion process.