Transport and endogenous release of vitamin B 12 in the dually perfused human placenta

Abstract

The kinetics for vitamin B 12, cobalamin (Cbl), transfer across the human placenta, and the retention of the endogenous Cbl and its release into the maternal and fetal compartments were investigated in a dually perfused human term placenta in vitro. After 4 hours of perfusion following a single bolus injection (peak maternal perfusate 94 fmol/ml) of 57Co-Cbl into the maternal reservoir, the maternal [ 57Co-Cbl] rapidly decreased whereas the fetal [ 57Co-Cbl] was only 9% of the final maternal [ 57Co-Cbl]. Even though there was a limited transfer of 57Co-Cbl to the fetus, the placenta rapidly accumulated Cbl. At 4 hours, 18% of the initial 57Co-Cbl dose was in the placenta; only 3% of the initial dose was in the fetal perfusate. Also after 4 hours, [ 57Co-Cbl] was bound >95% to transcobalamin (TC)I/III-like proteins in the maternal perfusate, whereas Cbl was bound to TCI/III- and TCII-like proteins with some free in the fetal perfusate. In the cytosol, >95% of the [ 57Co-Cbl] was bound (80% to TCII-like and 19% to TCI/III-like proteins). When no exogenous Cbl was added, total endogenous [Cbl] in the maternal circulation increased with time during 8 hours of perfusion at a rate of 0.25 ± 0.12 pmol/gm per hour. Only 2% of this Cbl was free, whereas 98% was bound to specific binding proteins. Neither plateau values nor equilibration with the fetal side were noted. In the fetal circulation, there was a release of Cbl at a rate of 0.015 ± 0.003 pmol/gm per hour, which was 99.99% bound. Thus the human placenta rapidly concentrates Cbl in the perfused lobule with little distribution of Cbl to nonperfused areas. Therefore, the human placenta modulates the asymmetric transfer of vitamin B 12 on the basis of release of specific Cbl-binding proteins (TCI/III- and TCII-like) into the maternal and fetal perfusates. (J Pediatr 1998;132:S35-S42.)