REGULATION OF INSULIN-LIKE GROWTH FACTOR-BINDING PROTEINS IN THE BABOON (PAPIO-ANUBIS) UTERUS DURING EARLY-PREGNANCY

The baboon uterus begins to synthesize insulin-like growth factor-bind ing protein-1 (IGFBP-1) in the deep glands of the late secretory endom etrium, and this protein then becomes the major secretory product of t he term decidua. We hypothesized that the placenta and/or conceptus ma y regulate the synthesis and secretion of IGFBP-1 by decidualized stro mal cells during pregnancy. To test this hypothesis, tissue was obtain ed from pregnant baboons on days 18, 25, and 32 postovulation. The ute rus was separated into three regions: RI (directly below the implantat ion site), RII (adjacent to the implantation site), and RIII (opposite the implantation site). Portions of the tissue were fixed in Bouin's solution for immunocytochemistry, and the remainder was subdivided int o functionalis, basalis, and myometrium and subjected to organ explant culture. The placenta was fixed or cultured separately. Ligand blot a nalysis of functionalis medium showed that the major IGFBP had a mol w t (M(r)) of 29,000-31,000; however, a doublet of 37,000-43,000 M(r) an d a band at 24,000 M(r) were also present. The functionalis from all r egions expressed the majority of the IGFBPs, but basalis from RI tissu e also secreted the same array of IGFBPs on days 25 and 32. Ligand blo t analysis of placental medium proteins revealed a doublet at M(r) 37, 000-43,000 on days 25 and 32, but not on day 18. Immunoprecipitation f ollowed by ligand blot analysis of medium proteins using polyclonal an tibodies to IGFBP-1 and IGFBP-2 and -3 confirmed that IGFBP-1 and -2 w ere the predominant products of the endometrium and decidua, while IGF BP-3 was synthesized by the placenta. Immunocytochemistry with a monoc lonal antibody to IGFBP-1 demonstrated intense glandular epithelial st aining in all regions on days 18, 25, and 32. Stromal staining for IGF BP-1 was first evident on day 25 and was only present in stromal cells in intimate contact with the trophoblastic tissue. By day 32, IGFBP-1 expression was not limited to the endometrial-trophoblastic junction, but extended to the deeper stromal cells and included the perivascula r regions. IGFBP-1 staining was most intense in RI, but stromal cells at the luminal surface and those surrounding the spiral arteries also showed some staining in RII and RIII on day 32. These studies suggest that the baboon placenta and/or conceptus regulate IGFBP expression in the uterine endometrium during the initial stages of pregnancy. We pr opose that this regulation of glandular and stromal IGFBP synthesis at the placental/endometrial interface may be of physiological importanc e in trophoblast penetration and the establishment of syncytial contac t with the maternal vasculature.