FIBROBLAST GROWTH FACTOR-II (FGF-S) IS PRESENT IN MATERNAL AND CORD SERUM, AND IN THE MOTHER IS ASSOCIATED WITH A BINDING-PROTEIN IMMUNOLOGICALLY RELATED TO THE FGF RECEPTOR-1

Fibroblast growth factor-2 (FGF-2) is expressed in human fetal tissues and placenta. We, therefore, determined whether FGF-2 appeared in eit her fetal or maternal circulations during normal pregnancies [fetuses appropriate for gestational age (AGA)] or those complicated by fetal g rowth restriction (small for gestational age). Cordocentesis was perfo rmed, and matched maternal blood was collected between 19-39 weeks ges tation, whereas maternal and cord blood and amniotic fluid (AF) were c ollected at term. FGF-2 was extracted from maternal serum (MS), cord s erum (CS), and AF by heparin-Sepharose affinity chromatography and sub jected to Western blot analysis or quantified by specific RIA. Western blot analysis of MS, CS, and AF revealed, in each case, a single immu noreactive FGF-2 species of 18 kilodaltons (kDa), although this was no t present in nonpregnant serum. In AGA pregnancies, immunoreactive FGF -2 was present in MS from at least 18 weeks gestation and rose to maxi mum values at the end of second trimester (weeks 28-31; mean +/- SEM, 342 +/- 62 pmol/L), but by term had declined (weeks 40-42; 104 +/- 24 pmol/L). In CS, FGF-2 immunoreactivity was highest at weeks 18-20 of g estation (662 +/- 144 pmol/L), but thereafter, slowly declined to term (weeks 40-42; 119 +/- 28 pmo/L). Immunoreactive FGF-2 levels in MS an d CS of small for gestational age pregnancies in the second trimester tended to be lower than those in AGA pregnancies, but differences were not statistically significant. AF also contained immunoreactive FGF-2 at term (91 +/- 35 pmol/L). Neutral gel chromatography on Sephadex G- 200 revealed that FGF-2 immunoreactivity eluted as a broad peak with a n apparent molecular size of 55-160 kDa. These same fractions containe d peptides of 55-60, 90-95, and 120-130 kDa, which were recognized by antisera against the extracellular domain of the high affinity FGF rec eptor, FGFR1, after Western blot. Ligand blot analysis of the same nit rocellulose filters using I-125-labeled FGF-2 revealed that the 55- to 60-kDa species specifically bound FGF-2. This binding species was not recognized during Western blot analysis using an antiserum raised aga inst the intracellular tyrosine kinase domain of FGFR1, suggesting tha t it represents a truncated receptor form. Similar FGFR1 immunoreactiv e species were present in nonpregnant female and male sera, but were b arely detectable in term CS or AF. These results suggest that soluble FGF-2 is present in MS, CS, and AF, and that in MS, this circulates in complex with a binding protein(s) related to the extracellular domain of the high affinity receptor, FGFR1.