FIBROBLAST GROWTH-FACTOR-II AND FIBROBLAST GROWTH-FACTOR RECEPTOR-1 MESSENGER-RNA EXPRESSION AND PEPTIDE LOCALIZATION IN PLACENTAE FROM NORMAL AND DIABETIC PREGNANCIES

Fibroblast growth factor-2 (FGF-2) is a potent mitogen expressed widel y during embryogenesis and in tissues of the human fetus. It is recogn ized as an endothelial cell mitogen and is angiogenic in vivo. Express ion of FGF-2 mRNA has also been shown within the human term placenta, and FGF-2 isolated from placental tissue, suggesting a role in placent al growth including angiogenesis. The purpose of this study was to qua ntify and localize the sites of expression of FGF-2 and its high-affin ity receptor, FGFR1, within placentae from normal term human pregnanci es (n=8, 39-42 weeks), and pregnancies complicated by pregestational, type 1 diabetes (n=8, 36-40 weeks). Tissues were collected immediately following delivery and were either snap-frozen for RNA isolation, or fixed for either in situ hybridization using a S-35-labelled cRNAs enc oding human FGF-2 or FGFR1, or immunocytochemistry using antibodies ag ainst human FGF-2 or FGFR1. Northern blot hybridization showed a signi ficantly increased abundance of mRNAs for both FGF-2 and FGFR1. in pla centae from diabetic women compared to those from normal women. In nor mal term placenta FGF-2 mRNA was present at low abundance in fetal vil lous tissue, in the vascular endothelium of blood vessels, and in the syncytiotrophoblast. FGF-2 mRNA was considerably more abundant in the syncytiotrophoblast and villous tissue of placentae from diabetic pati ents. Messenger RNA for FGFR1 was similarly distributed to that encodi ng FGF-2. Immunocytochemistry revealed abundant FGF-2 and FGFR1 peptid es in villous vascular endothelial cells, and associated with the cell membranes of stromal tissues in placentae from control pregnancies. L ittle immunoreactive FGF-2 was present in the syncytiotrophoblast at t erm. In pregnancies complicated by diabetes intense staining for immun oreactive FGF-2 and for FGFR1 additionally existed in syncytiotrophobl ast. The results suggest that FGF-2 acting as an autocrine agent contr ibutes to placental angiogenesis, but may be released from the syncyti um into the maternal circulation. Expression is elevated in placentae from diabetic pregnancies, and is particularly associated with the syn cytiotrophoblast. This suggests a placental source for the elevated ci rculating maternal FGF-2 previously described in diabetic pregnancy. ( C) 1998 W.B. Saunders Company Ltd.