Increased N-glycosylation and reduced transferrin-binding capacity of transferrin receptor isolated from placentae of diabetic women

Infants of diabetic mothers are frequently born iron deficient because their fetal iron demand exceeds placental iron transport capacity. Although transferrin receptor (TfR) expression is increased, binding to diferric transferrin is decreased proportionately to the severity of maternal disease. It is hypothesized that TfR isolated from diabetic placentae has altered N-glycosylation since proper glycosylation of N-linked oligosaccharides is important for normal TW binding kinetics to diferric transferrin. TfR was obtained from syncytiotrophoblastic membranes of six diabetic and sis non-diabetic human placentae. Competitive binding to I-125-transferrin demonstrated a higher K-d in the diabetic TfR (P=0.04), directly correlated to cord serum C-peptide concentration (r=0.81, P<0.001). The molecular weight of the monomeric form of TfR prior to treatment with glycopeptidase F (PNG-F) was greater in the diabetic group (P<0.001) and was directly related to the K, (r=0.77, P=0.002). Treatment with PNG-F eliminated the molecular weight difference between the two groups. Increased glycosylation of the N-linked oligosaccharides of TfR isolated from diabetic placentae may alter the three-dimensional structure or charge of the receptor, thus reducing its binding affinity for transferrin. (C) 1997 W.B. Saunders Company Ltd.