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

• Published in: Pediatric research Vol. 45; no. 6; pp. 860 - 866
• Main Authors: AIMONE-GASTIN, I, GUEANT, J. L, PLENAT, F, MUHALE, F, MAURY, F, DJALALI, M, GERARD, P, DUPREZ, A
• Format: Conference Proceeding Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-06-1999
• Subjects: Amniotic Fluid - metabolism; Animals; Biological and medical sciences; Biological Transport, Active; Carrier Proteins - metabolism; Cobalt Radioisotopes; Digestive System - embryology; Digestive System - metabolism; Embryology: invertebrates and vertebrates. Teratology; Female; Fundamental and applied biological sciences. Psychology; Humans; Intestinal Absorption; Intestinal Mucosa - metabolism; Intestines - transplantation; Intrinsic Factor - metabolism; Mice; Mice, Nude; Organogenesis. Physiological fonctions; Physiological fonctions; Pregnancy; Stomach - transplantation; Transplantation, Heterologous; Vitamin B 12 - metabolism; Vitamin B 12 - pharmacokinetics; Human; Stomach; Animal model; Rodentia; Gut; Transplantation; Biosynthesis; Heterotransplantation; Vertebrata; Intrinsic factor; Regulation(control); Mammalia; Absorption; Mouse; Surgery; Amniotic fluid; Fetus; Cobalamine
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1203/00006450-199906000-00014

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.