IGF binding protein-1 (IGFBP-1) is preferentially associated with the fetal facing basal surface of the syncytiotrophoblast in the human placenta

IGF receptors are expressed in a spatially polarized manner on the syncytio trophoblast cell membrane. We therefore examined the hypothesis that IGFBPs expressed at the maternal-fetal interface interact with distinct surfaces of the syncytiotrophoblast membrane to modulate IGF function. Membrane vesi cles were prepared specifically from the maternal-facing, microvillous memb rane (MVM) and the fetal-facing, basal membrane (BM) surfaces of the syncyt iotrophoblast. The association of IGFBPs with each membrane preparation was determined by ligand blot analysis. A doublet migrating at 38/42 kD was de tected in both MVM and BM preparations. Selective immunoprecipitation follo wed by ligand blot analysis identified this IGF binding species as IGFBP-3. Additionally, a protein migrating at approximately 29 kD was associated pr imarily with the BM. This protein was identified as IGFBP-1 by both immunop recipitation and ligandblotting techniques. Non-denaturing PAGE revealed fi ve distinct bands corresponding to different degrees of phosphorylation, Th e phosphorylation pattern of BM-associated IGFBP-1 was identical to that of native IGFBP-1 in amniotic fluid. Immunohistological analysis of term plac enta revealed IGFBP-1-specific staining of the syncytiotrophoblast and the fetal capillary/pericapillary bed. The localization of IGFBP-1 to a distinc t compartment within the fetal placenta, not in proximity to the syncytiotr ophoblast type I IGF receptor, suggests it may play a role in regulating/ta rgeting IGF activity within the stromal compartment or by exerting IGF-inde pendent effects on the basal surface of the syncytiotrophoblast. The nature of its binding to the BM has not been determined. (C) 1999 Harcourt Publis hers Ltd.