Localization of insulin-like growth factor binding protein-4 expression in the mouse uterus during the peri-implantation period.

Previous studies have suggested a role for insulin-like growth factors (IGFs) in both embryo and trophoblast growth, as well as in uterine differentiation. Included in the IGF family are the IGF binding proteins (IGFBPs). In the current study we have demonstrated, by Western ligand 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-implantation 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, IGFBP-4 mRNA was present in the uterine stroma underlying the luminal epithelium. By gestational Day 6, approximately 24 h after implantation, a IGFBP-4 mRNA signal was intense at each implantation site and extended throughout the decidua. A signal was absent in the uterine tissue between implantation sites. By gestational Day 8, the IGFBP-4 mRNA signal 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 implantation process.