title: Assimilation of [57Co]-labeled cobalamin in human fetal gastrointestinal xenografts into nude mice.
abstract: 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 [57Co]-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 IF [57Co]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-[57Co]Cbl-IF or cyano-[57Co]Cbl, respectively, was instilled in intestinal grafts. Chloroquine reduced significantly the percentage of excreted [57Co]Cbl. The [57Co]Cbl was mainly excreted as cyano-[57Co]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.
authors.affiliation: Cellular and Molecular Pathology in Nutrition, Faculté de Médecine de Nancy, Université H. Poincaré, Vandoeuvre lès Nancy, France.
authors.forename: I
authors.initials: I
authors.lastname: Aimone-Gastin
authors.forename: J L
authors.initials: JL
authors.lastname: Gueant
authors.forename: F
authors.initials: F
authors.lastname: Plenat
authors.forename: F
authors.initials: F
authors.lastname: Muhale
authors.forename: F
authors.initials: F
authors.lastname: Maury
authors.forename: M
authors.initials: M
authors.lastname: Djalali
authors.forename: P
authors.initials: P
authors.lastname: Gerard
authors.forename: A
authors.initials: A
authors.lastname: Duprez
mesh_terms: D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000378:metabolism; D003037:Cobalt Radioisotopes; D004064:Digestive System / Q000196:embryology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000637:transplantation*; D007437:Intrinsic Factor / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D011247:Pregnancy; D013270:Stomach / Q000637:transplantation*; D014183:Transplantation, Heterologous; D014805:Vitamin B 12 / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D002352:Carrier Proteins; D003037:Cobalt Radioisotopes; D007437:Intrinsic Factor; D014805:Vitamin B 12