Genetic evidence for fetal origin of transcobalamin II in human cord blood.

Phenotypes of transcobalamin II (TC2) were determined in 95 maternal-cord serum pairs in order to identify the origin of TC2 in human cord blood. Unsaturated (apo) TC2 in serum was labeled with radioactive (57Co) cobalamin (CbI) and separated into isoproteins by polyacrylamide gel electrophoresis and autoradiography. Discordancy between the maternal and the cord serum type was observed in 45% of the pairs. The results demonstrated that, at the end of pregnancy, the fetus is capable of TC2 synthesis and that there is no detectable transplacental passage of maternal apo-TC2. Presence of maternal saturated (holo) TC2 in cord serum could be excluded in 9 informative discordant pairs by exchanging endogenously bound CbI with 57Co-CbI. Our finding that TC2 in human cord serum is of fetal rather than maternal origin suggests an essential role for fetal TC2 in CbI utilization and appears to contradict the hypothesis that transplacental passage of maternal TC2 may explain the normal fetal development in cases of congenital TC2 deficiency. The total immunoreactive TC2 content in 23 maternal serum samples collected at the end of pregnancy (812 +/- 175 pM CbI equivalent) was significantly higher than in the corresponding cord sera (605 +/- 148 pM; p less than 0.001) and did not significantly differ from the value in a control group of healthy male and female adults (841 +/- 192 pM). At the end of pregnancy, the apo-TC2 content in 12 maternal serum samples (760 +/- 347 pM) was significantly higher than in the corresponding cord sera (501 +/- 254 pM; p less than 0.05) and did not significantly differ from the value in the control group (747 +/- 137 pM).