GESTATIONAL AGE-DEPENDENT EXPRESSION OF INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-1 (IGFBP-1) PHOSPHOISOFORMS IN HUMAN EXTRAEMBRYONIC CAVITIES, MATERNAL SERUM, AND DECIDUA SUGGESTS DECIDUA AS THE PRIMARY SOURCE OF IGFBP-1 IN THESE FLUIDS DURING EARLY-PREGNANCY

The insulin-like growth factors (IGFs) and their binding proteins (IGF BPs) are important regulators of fetal and maternal tissue development during pregnancy. Posttranslational modification of IGFBP-1 yields up to six IGFBP-1 phosphovariants and a nonphosphorylated form, which in vitro, have some different properties. Non phospho IGFBP-1 has less a ffinity for IGFs than the phospho isoforms and also may have IGF-indep endent actions. Herein, we have investigated the complement of IGFBP-1 phosphoisoforms present in extraembryonic coelomic (EEC) fluid, amnio tic fluid (AF), and maternal serum (MS) throughout human gestation. Al so, to determine potential tissue source(s) of IGFBP-1 in these fluids , we have quantified IGFBP-1 and examined IGFBP-1 phosphoisoforms in c onditioned media (CM) from maternal decidua, fetal liver, and fetal ki dney explants throughout gestation. Western immunodetection revealed t hat IGFBP-1, present in EEC and AF in early pregnancy and in CM from e arly pregnancy decidua, is primarily in the nonphosphorylated form. MS in this period contains primarily the nonphospho form and, as in nonp regnant adults, the highly phosphorylated form of IGFBP-1. The phospho rylation profile of IGFBP-1 in AF, MS, and decidua CM changes as pregn ancy progresses. All the IGFBP-1 phosphoisoforms ultimately are produc ed by decidua and are present in midgestation MS, and all but the most highly phosphorylated form are present in AF. In late gestation, MS c ontains primarily the highly phosphorylated form. In contrast, profile s in CM from explants of fetal liver and kidney at different gestation al ages remain unchanged. Nonphosphorylated IGFBP-1 is the primary for m in fetal kidney CM, whereas fetal liver CM contains all IGFBP-1 phos phoisoforms. Concentrations of IGFBP-1 in fetal liver and kidney CM ar e significantly lower (482 +/- 146 and 120 +/- 32 ng/mL.100 mg wet wt tissue, respectively) than in decidua CM (11,417 +/- 2,358 ng/mL.100 m g wet wt tissue). The data cumulatively suggest that maternal decidua is the primary source of IGFBP-1 in EEC, AF, and MS in early pregnancy and that fetal liver and kidney are not likely significant contributo rs. The presence of nonphospho IGFBP-1 in AF, EEC, and MS suggests an important role for this isoform during early gestation.