Insulin-like growth factor binding protein concentration and post- translational modification in embryological fluid

Levels of proteolytic activity directed against insulin-like growth factorbinding protein 3 (IGFBP-3) and the distribution of phosphorylated isoformsof IGFBP-1 were assessed in matched sample sets of maternal serum, coelomicfluid and amniotic fluid from 21 pregnancies at 6-12 weeks gestation. Inaddition, concentrations of immunoreactive IGFBP-1 to -3, insulin-likegrowth factor (IGF)-I and - II were determined in all three compartments in21 pregnancies, and in coelomic fluid and maternal serum in 58 pregnancies.IGF-I concentrations were highest in maternal serum and similarly low incoelomic and amniotic fluid. IGF-II concentrations were also highest inmaternal serum but easily detectable in coelomic fluid where concentrationsshowed a significant correlation with gestational age. IGFBP-1concentrations were higher in coelomic fluid than in either maternal serumor amniotic fluid and showed a significant correlation with gestational agein this compartment. Analysis of IGFBP-1 phosphoforms showed cleardifferences in phosphorylation of IGFBP-1 between groups with maternalserum containing predominantly the phosphorylated forms and coelomic fluidalmost exclusively the non- phosphorylated form. First trimester amnioticfluid IGFBP-1 was barely detectable and appeared non-phosphorylated. Thesefindings suggest that the high IGF-II concentrations and lack of inhibitoryphosphoforms of IGFBP-1 in coelomic fluid could potentially enhancemitogenic activity in the early human gestational sac. IGFBP-2concentrations were high in coelomic fluid compared with maternal serumwhereas coelomic fluid IGFBP-3 concentrations were intermediate, easilydetectable and correlated strongly with gestational age. Protease activitywas far less in coelomic fluid than in matched maternal serum samples.Marked differences in both concentrations and post-translationalmodification of IGFBPs in maternal serum compared with embryonic fluidsuggest different regulatory pathways.