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.