I. Aimone-gastin et al., Assimilation of [Co-57]-labeled cobalamin in human fetal gastrointestinal xenografts into nude mice, PEDIAT RES, 45(6), 1999, pp. 860-866
Cobalamin (Cbl) and its Cbl-binding proteins are present in amniotic fluid.
Because amniotic fluid is swallowed by the embryo-fetus, we studied the ab
ility of Cbl to be transported and metabolized across the embryo-fetal dige
stive 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 gas
tric mucosa by immunohistochemistry. The uptake of [Co-57]-labeled Cbl by t
he intestinal graft was studied by Schilling tests and HPLC. IF, haptocorri
n, and a transcobalamin-like protein were detected in gastric juice, with c
oncentration ranges of 5.0-26.4, 1.9-27.1, and 5.2-12.6 pmol/ml, respective
ly. The 1F [Co-57]Cbl complex had a single isoprotein with a pi at 5.6, whi
ch was maintained after incubation with neuraminidase. Urine excretion perc
entages (Schilling tests) ranged from 5.5 to 21.2% and from 0.3 to 1.6% whe
n cyano-[Co-57]Cbl-IF or cyano[Co-57]Cbl, respectively, was instilled in in
testinal grafts. Chloroquine reduced significantly the percentage of excret
ed [Co-57]Cbl. The [Co-57]Cbl was mainly excreted as cyano[Co-57]Cbl in uri
nes, showing a low coenzyme conversion. In conclusion, IF is secreted by th
e nonstimulated embryonic stomach and lacks sialic acid. Cbl binds to it an
d is subsequently transported across the xenografted embryo-fetal intestine
. This suggests that amniotic fluid may contribute to Cbl delivery to the e
mbryo-fetus.