title: Monoclonal antibody directed to Le(y) oligosaccharide inhibits implantation in the mouse.
abstract: We investigated the role of carbohydrates in blastocyst attachment to the uterine epithelium. Le(y) (Fuc alpha 1-->2Gal beta 1-->4[Fuc alpha 1-->3] GlcNAc) was localized by indirect immunofluorescence to the surface of the mouse blastocyst and uterine epithelium. Western blot analysis showed that Le(y) is carried on many uterine glycoproteins in both pregnant and nonpregnant females; however, new species were detected on Day 4 postcoitum (p.c.) coincident with the onset of uterine receptivity. The function of Le(y) in implantation was tested by injecting monoclonal antibody (mAb) directly into the uterine lumen on Days 3-5 p.c. The effects of intrauterine injections on implantation were scored by comparing the number of viable embryos to the number of CL on Day 10 p.c. Injection of purified anti-Le(y) IgM into the uterine lumen on the afternoon of Day 4 significantly inhibited implantation. This effect was dose-dependent and was obtained during a narrow time window, from 87 to 93 h p.c. Inhibition of implantation was not observed in contralateral uterine horns injected with saline, nor was it observed in uterine horns injected with other anti-carbohydrate mAbs. We conclude that binding of anti-Le(y) to the blastocyst or luminal epithelium masks a ligand involved in implantation. Although the mechanism of inhibition is unknown, we show that Le(y) can interact with another oligosaccharide (H) that has been described as a possible uterine ligand for blastocyst attachment. We hypothesize that Le(y) and H form carbohydrate-carbohydrate interactions that promote close apposition of cell surface membranes during an early step in implantation.
authors.affiliation: Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical College Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Z M
authors.initials: ZM
authors.lastname: Zhu
authors.forename: N
authors.initials: N
authors.lastname: Kojima
authors.forename: M R
authors.initials: MR
authors.lastname: Stroud
authors.forename: S
authors.initials: S
authors.lastname: Hakomori
authors.forename: B A
authors.initials: BA
authors.lastname: Fenderson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D000943:Antigens, Differentiation / Q000032:analysis; D001755:Blastocyst / Q000502:physiology; D002240:Carbohydrate Sequence; D010064:Embryo Implantation / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D007075:Immunoglobulin M / Q000008:administration & dosage / Q000494:pharmacology; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D014599:Uterus / Q000737:chemistry / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D007075:Immunoglobulin M; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; C094162:Lewis Y antigen