title: Heparin-binding epidermal growth factor and its receptor ErbB4 mediate implantation of the human blastocyst.
abstract: The mechanisms that mediate implantation of the human embryo remain poorly understood and represent a fundamental problem in reproductive biology. Candidate molecules that mediate and facilitate implantation have been identified in animal studies, and include heparin binding epidermal growth factor. Here we demonstrate a potential function for the transmembrane form of heparin-binding epidermal growth factor in mediating blastocyst attachment to the endometrium, in two different novel in vitro models for human implantation. Furthermore, we demonstrate specific localisation of the heparin-binding epidermal growth factor receptor ErbB4, on the surface of the trophectoderm in peri-implantation human blastocysts. Our data lead the way for further dissection of the molecular mechanisms of implantation of the human embryo, and have implications for infertility, in vitro fertilization and contraception.
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, The Women's Centre, Level 3, John Radcliffe Hospital, University of Oxford, Headington, Oxford, OX3 9DU, UK.
authors.forename: Katya
authors.initials: K
authors.lastname: Chobotova
authors.forename: Isabella
authors.initials: I
authors.lastname: Spyropoulou
authors.forename: Janet
authors.initials: J
authors.lastname: Carver
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Manek
authors.forename: John K
authors.initials: JK
authors.lastname: Heath
authors.forename: William J
authors.initials: WJ
authors.lastname: Gullick
authors.forename: David H
authors.initials: DH
authors.lastname: Barlow
authors.forename: Ian L
authors.initials: IL
authors.lastname: Sargent
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Mardon
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D004591:Electrophoresis, Polyacrylamide Gel; D010064:Embryo Implantation; D004717:Endometrium / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D066247:Receptor, ErbB-4; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor; D006493:Heparin; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4