title: The human blastocyst regulates endometrial epithelial apoptosis in embryonic adhesion.
abstract: The implanting blastocyst must appose and adhere to the endometrial epithelium and, subsequently, invade it. Locally regulated uterine epithelial apoptosis induced by the embryo is a crucial step of the epithelial invasion in rodents. To address the physiological relevance of this process in humans, we investigated the effect of single human blastocysts on the regulation of apoptosis in cultured human endometrial epithelial cells (hEEC) in both apposition and adhesion phases of implantation. Here, we report a co-ordinated embryonic regulation of hEEC apoptosis. In the apposition phase, the presence of a blastocyst rescues hEEC from the apoptotic pathway. However, when the human blastocyst adheres to the hEEC monolayer, it induces a paracrine apoptotic reaction. Fas ligand (Fas-L) was present at the embryonic trophoectoderm. Fas was localized at the apical cell surface of hEEC, and flow cytometry revealed that 60% of hEEC express Fas. Neutralizing adhesion assays revealed that the Fas/Fas-L death system may be an important mechanism to cross the epithelial barrier, which is crucial for embryonic adhesion, and the manipulation of this system could have potential clinical implications as an interceptive mechanism.
authors.affiliation: Instituto Valenciano de Infertilidad, 46020 Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Galán
authors.forename: J E
authors.initials: JE
authors.lastname: O'Connor
authors.forename: D
authors.initials: D
authors.lastname: Valbuena
authors.forename: R
authors.initials: R
authors.lastname: Herrer
authors.forename: J
authors.initials: J
authors.lastname: Remohí
authors.forename: S
authors.initials: S
authors.lastname: Pampfer
authors.forename: A
authors.initials: A
authors.lastname: Pellicer
authors.forename: C
authors.initials: C
authors.lastname: Simón
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001755:Blastocyst / Q000502:physiology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D018920:Coculture Techniques; D010064:Embryo Implantation / Q000502:physiology*; D004624:Embryo Transfer; D004717:Endometrium / Q000166:cytology*; D004847:Epithelial Cells / Q000502:physiology; D053222:Fas Ligand Protein; D005260:Female; D005307:Fertilization in Vitro; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D008562:Membrane Glycoproteins / Q000032:analysis; D010718:Phosphatidylserines / Q000032:analysis; D019014:fas Receptor / Q000032:analysis
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D010718:Phosphatidylserines; D019014:fas Receptor