title: MUC16 is lost from the uterodome (pinopode) surface of the receptive human endometrium: in vitro evidence that MUC16 is a barrier to trophoblast adherence.
abstract: In order for the preimplantation embryo to implant into the uterus, the trophoblast cells must initially adhere to the uterine epithelial surface. In preparation, the luminal secretory cells of the epithelium lose their nonadhesive character and their surface microvilli and bulge into the lumen, forming uterodomes (pinopodes; uterodome is used instead of pinopode, since in humans the surface membrane exocytoses rather than endocytoses (Murphy, Hum Reprod 2000; 15:2451-2454). Previous research has led to the hypothesis that loss of the nonadhesive membrane-spanning mucin MUC1 from the uterodome surface allows trophoblast adherence. Immunofluorescence microscopic assay of luminal epithelia on human uterine biopsies taken from LH+0 to LH+13 show that another membrane-spanning mucin, MUC16, was lost from uterodome surfaces in all samples taken during the receptive phase, LH+6 to LH+8 (n = 12), and that MUC1 was present on uterodomes in 4 of 12 samples and on all ciliated cells of the epithelium in the receptive phase. Short interfering RNA (siRNA) knockdown of MUC16 in a uterine epithelial cell line ECC-1 that, like uterine epithelium, expresses MUC16 and MUC1 allowed increased adherence of cells of a trophoblast cell line. In parallel experiments, siRNA knockdown of MUC1 did not affect trophoblast cell adherence. These data indicate that MUC16 is a membrane component of the nonreceptive luminal uterine surface, which prevents cell adhesion, and that its removal during uterodome formation facilitates adhesion of the trophoblast.
authors.affiliation: Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA. ilene.gipson@schepens.harvard.edu
authors.forename: Ilene K
authors.initials: IK
authors.lastname: Gipson
authors.forename: Timothy
authors.initials: T
authors.lastname: Blalock
authors.forename: Ann
authors.initials: A
authors.lastname: Tisdale
authors.forename: Sandra
authors.initials: S
authors.lastname: Spurr-Michaud
authors.forename: Sara
authors.initials: S
authors.lastname: Allcorn
authors.forename: Anneli
authors.initials: A
authors.lastname: Stavreus-Evers
authors.forename: Kristina
authors.initials: K
authors.lastname: Gemzell
mesh_terms: D000328:Adult; D018394:CA-125 Antigen / Q000378:metabolism*; D002448:Cell Adhesion; D002460:Cell Line; D004717:Endometrium / Q000378:metabolism*; D004848:Epithelium / Q000502:physiology; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D018396:Mucin-1 / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D046509:Tissue Culture Techniques; D014327:Trophoblasts / Q000502:physiology*
chemical_list: D018394:CA-125 Antigen; C060192:MUC1 protein, human; C451759:MUC16 protein, human; D008565:Membrane Proteins; D018396:Mucin-1; D012333:RNA, Messenger