Assimilation of [57Co]-labeled cobalamin in human fetal gastrointestinal xenografts into nude mice

Cobalamin (Cbl) and its Cbl-binding proteins are present in amniotic fluid. Because amniotic fluid is swallowed by the embryo-fetus, we studied the ability of Cbl to be transported and metabolized across the embryo-fetal digestive tract. Human embryonic stomachs and intestines were transplanted into nude mice. The basal secretion of Cbl-binding proteins was studied by gel filtration of the graft juices. intrinsic factor (IF) was looked for in gastric mucosa by immunohistochemistry. The uptake of [Co-57]-labeled Cbl by the intestinal graft was studied by Schilling tests and HPLC. IF, haptocorrin, and a transcobalamin-like protein were detected in gastric juice, with concentration ranges of 5.0-26.4, 1.9-27.1, and 5.2-12.6 pmol/ml, respectively. The 1F [Co-57]Cbl complex had a single isoprotein with a pi at 5.6, which was maintained after incubation with neuraminidase. Urine excretion percentages (Schilling tests) ranged from 5.5 to 21.2% and from 0.3 to 1.6% when cyano-[Co-57]Cbl-IF or cyano[Co-57]Cbl, respectively, was instilled in intestinal grafts. Chloroquine reduced significantly the percentage of excreted [Co-57]Cbl. The [Co-57]Cbl was mainly excreted as cyano[Co-57]Cbl in urines, showing a low coenzyme conversion. In conclusion, IF is secreted by the nonstimulated embryonic stomach and lacks sialic acid. Cbl binds to it and is subsequently transported across the xenografted embryo-fetal intestine. This suggests that amniotic fluid may contribute to Cbl delivery to the embryo-fetus.