Placental transferrin receptor in diabetic pregnancies with increased fetal iron demand.
Augmented fetal hemoglobin synthesis during diabetic pregnancy increases fetal iron demand. To study the effect of increased fetal iron demand on placental transferrin receptor (TR), we utilized a monoclonal antibody to localize placental TR immunoreactivity and 125I-labeled transferrin to study TR binding characteristics in 10 placentas from poorly controlled diabetic mothers with increased fetal iron demand and 10 placentas from nondiabetic mothers. The infants born to the diabetics had higher cord serum C-peptide, erythropoietin, and hemoglobin concentrations, indicating fetal hyperinsulinemia and hypoxia, with augmented erythropoiesis and iron demand. TR immunoreactivity was localized to the syncytiotrophoblast in both groups, was greater in the diabetic group, and was inversely correlated with fetal storage iron (r = -0.75; P < 0.001). Scatchard analysis of 125I transferrin binding data confirmed greater receptor number (Bmax 17.9 +/- 2.2 vs. 12.6 +/- 1.3 pM/mg protein, P = 0.05), but reduced binding affinity [dissociation constant (Kd) 7.6 +/- 0.9 vs. 5.4 +/- 0.4 nM/l, P = 0.03] in the diabetic group. The TR staining intensity, Bmax, and Kd were each correlated with cord C-peptide, suggesting either a primary or secondary role for fetal hyperinsulinemia in TR expression. This study provides in vivo evidence that fetal factors, such as iron demand or hyperinsulinemia, influence regulation of placental TR in humans. The increase in placental syncytiotrophoblastic TR expression associated with reduced cord serum ferritin concentration suggests that the fetus utilizes both increased placental iron transport and mobilization of fetal iron stores to support augmented fetal erythropoiesis.
Petry
C D
CD
Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis 55455.
Wobken
J D
JD
McKay
H
H
Eaton
M A
MA
Seybold
V S
VS
Johnson
D E
DE
Georgieff
M K
MK
D004920:Erythropoiesis; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn / Q000378:metabolism; D007328:Insulin; D007501:Iron / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism
D007328:Insulin; D011990:Receptors, Transferrin; D014168:Transferrin; D007501:Iron