The human blastocyst regulates endometrial epithelial apoptosis in embryonic adhesion

The implanting blastocyst must appose and adhere to the endometrial epithel ium and, subsequently, invade it. Locally regulated uterine epithelial apop tosis 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 o f apoptosis in cultured human endometrial epithelial cells (hEEC) in both a pposition and adhesion phases of implantation Here, we report a co-ordinate d embryonic regulation of hEEC apoptosis. In the apposition phase, the pres ence 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 tropho ectoderm. Fas was localized at the apical cell surface of hEEC, and flow cy tometry 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.