title: Estrogen-dependent uterine secretion of osteopontin activates blastocyst adhesion competence.
abstract: Embryo implantation is a highly orchestrated process that involves blastocyst-uterine interactions. This process is confined to a defined interval during gestation referred to as the "window of embryo implantation receptivity". In mice this receptive period is controlled by ovarian estrogen and involves a coordination of blastocyst adhesion competence and uterine receptivity. Mechanisms coordinating the acquisition of blastocyst adhesion competence and uterine receptivity are largely unknown. Here, we show that ovarian estrogen indirectly regulates blastocyst adhesion competence. Acquisition of blastocyst adhesion competence was attributed to integrin activation (e.g. formation of adhesion complexes) rather than de novo integrin synthesis. Osteopontin (OPN) was identified as an estrogen-dependent uterine endometrial gland secretory factor responsible for activating blastocyst adhesion competence. Increased adhesion complex assembly in OPN-treated blastocysts was mediated through focal adhesion kinase (FAK)- and phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathways. These findings define for the first time specific regulatory components of an estrogen-dependent pathway coordinating blastocyst adhesion competence and uterine receptivity.
authors.affiliation: Laboratory of Animal Breeding, Department of Veterinary Medical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Chaen
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Konno
authors.forename: Mahiro
authors.initials: M
authors.lastname: Egashira
authors.forename: Rulan
authors.initials: R
authors.lastname: Bai
authors.forename: Nana
authors.initials: N
authors.lastname: Nomura
authors.forename: Shintaro
authors.initials: S
authors.lastname: Nomura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hirota
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sakurai
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Imakawa
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism*; D002448:Cell Adhesion; D003656:Decidua / Q000502:physiology; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D016023:Integrins / Q000378:metabolism; D051379:Mice; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction; D014599:Uterus / Q000378:metabolism*
chemical_list: D004967:Estrogens; D005353:Fibronectins; D016023:Integrins; D053495:Osteopontin; D019869:Phosphatidylinositol 3-Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases