Several endometrial signal transducer and activator of transcription 3 (STAT3)-activating cytokines are reported to be essential for blastocyst implantation, with inhibition of STAT3 activation in the endometrium also reported to prevent implantation. To investigate STAT3 signals in endometrial epithelial cells, the activation and inactivation effects of STAT3 signals were examined in the human endometrial epithelial cell line HHUA, which is thought to retain many of the intracellular signaling pathways found in normal human endometrial epithelial cells. Five STAT3-activating cytokines, IL-11, IL-10, LIF, oncostatin M and leptin, enhanced the Fas-mediated apoptosis of the HHUA cells without any increase in cell surface Fas antigen expression. STAT3 siRNA transfection suppressed STAT3 expression in HHUA cells and significantly inhibited Fas-mediated cell death. These results indicate that intracellular apoptotic signals in HHUA cells are constitutively activated and regulated by STAT3-mediated signals. This apoptosis-promoting effect of STAT3 in HHUA cells is completely different from many previous reports demonstrating anti-apoptotic effects by STAT3 activation. The STAT3 signals in HHUA cells may be specific to the human endometrial epithelial cell lineage in the regulation of blastocyst implantation.

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