科研之友
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摘要
In species with hemochorial placentation, such as the mouse and human, trophoblast cells of the implanting blastocyst induce apoptosis and displace endometrial epithelial cells (EEC) to cross the luminal epithelium of the endometrium. Since Fas and Fas ligand (FasL) are expressed in EEC and trophoblast cells respectively and mitogen-activated protein kinases (MAPKs) mediate Fas-induced apoptosis, the roles of Fas/FasL and MAPK signaling in trophoblast-EEC interactions were studied. By co-culturing BeWo trophoblast spheroids with RL95-2 EEC monolayers to mimic blastocyst-endometrial interactions, we found that trophoblast spheroid outgrowth on EEC was significantly enhanced by anti-Fas activating antibody. Since anti-Fas activating antibody had no effect on spheroid expansion on EEC-free culture surfaces, its enhancing effect on spheroid outgrowth on EEC may be mediated by acting on EEC to facilitate trophoblast-induced EEC apoptosis and displacement. Valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (VAD-FMK) staining showed that the percentage of apoptotic EEC at the spheroid-EEC interface was markedly increased by anti-Fas activating antibody. Moreover, the pancaspase inhibitor benzyloxycarbonyl-VAD-FMK was able to suppress the enhancing effect of anti-Fas activating antibody on spheroid expansion on EEC. Upon anti-Fas activating antibody stimulation, both p38 MAPK and c-Jun NH2-terminal kinase (CNK) were activated. Furthermore, the anti-Fas activating antibody-enhanced EEC apoptosis and spheroid expansion on EEC were significantly inhibited by the p38 MAPK inhibitor SB203580 and JNK inhibitor SP600125. Our results establish that anti-Fas activating antibody could activate p38 MAPK and INK to induce EEC apoptosis, thereby promoting trophoblast outgrowth on EEC.
- 出版日期2008-4
