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Updated: Jul 10, 2026
Isolation of Human Endometrial Stromal Cells for In Vitro Decidualization
Published on: September 1, 2018
Interferon-gamma and tumor necrosis factor-alpha sensitize primarily resistant human endometrial stromal cells to
Herbert Fluhr1, Stefanie Krenzer, Gerburg M Stein
1Department of Obstetrics and Gynecology, University of Greifswald, Wollweberstr. 1, 17475 Greifswald, Germany.
Abstract:
The subtle interaction between the implanting embryo and the maternal endometrium plays a pivotal role during the process of implantation. Human endometrial stromal cells (ESCs) express Fas and the implanting trophoblast cells secrete Fas ligand (FASLG, FasL), suggesting a possible role for Fas-mediated signaling during early implantation. Here we show that ESCs are primarily resistant to Fas-mediated apoptosis independently of their state of hormonal differentiation. Pre-treatment of ESCs with interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha sensitizes them to become apoptotic upon stimulation of Fas by an agonistic anti-Fas antibody. Incubation of ESCs with the early embryonic signal human chorionic gonadotropin (hCG, CGB) does not influence their reaction to Fas stimulation. The sensitizing effect of IFN-gamma and TNF-alpha was accompanied by a significant upregulation of Fas and FLICE-inhibitory protein (FLIP, CFLAR) expression in ESCs. Additionally, we observed an activation of caspase 3, caspase 8 and caspase 9 upon apoptotic Fas triggering. In summary, we demonstrate that IFN-gamma and TNF-alpha sensitize primarily apoptosis-resistant ESCs to Fas-mediated cell death. This might be due to an upregulation of Fas expression, and apoptosis seems to be mediated by active caspase 3, caspase 8 and caspase 9. The observed pro-apoptotic effect of IFN-gamma and TNF-alpha on ESCs could play an important role in the modulation of early implantation.
Insights
Interferon-gamma and tumor necrosis factor-alpha sensitize human endometrial stromal cells (ESCs) to Fas-mediated apoptosis, potentially influencing early embryo implantation. These cytokines upregulate Fas and FLIP, activating caspases for cell death.
Area of Science:
- Reproductive Biology
- Cellular and Molecular Biology
- Immunology
Background:
- Embryo implantation involves complex interactions between the embryo and maternal endometrium.
- Human endometrial stromal cells (ESCs) express Fas, and trophoblast cells secrete Fas ligand (FASLG), suggesting Fas-mediated signaling in implantation.
- ESCs are generally resistant to Fas-mediated apoptosis, a crucial factor in early pregnancy.
Purpose of the Study:
- To investigate the role of Fas-mediated signaling in human endometrial stromal cells during early implantation.
- To determine the effect of cytokines interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) on ESC apoptosis.
- To explore the influence of human chorionic gonadotropin (hCG) on ESC response to Fas stimulation.
Main Methods:
- Treatment of ESCs with IFN-γ and TNF-α.
- Stimulation of Fas signaling using an agonistic anti-Fas antibody.
- Analysis of apoptosis, gene expression (Fas, FLIP), and caspase activation (caspase 3, 8, 9).
Main Results:
- ESCs are resistant to Fas-mediated apoptosis, irrespective of hormonal differentiation.
- IFN-γ and TNF-α pre-treatment sensitize ESCs to Fas-induced apoptosis.
- hCG does not affect ESCs' response to Fas stimulation; IFN-γ and TNF-α upregulate Fas and FLIP, activating caspases 3, 8, and 9.
Conclusions:
- IFN-γ and TNF-α sensitize apoptosis-resistant ESCs to Fas-mediated cell death.
- This sensitization is linked to upregulated Fas expression and caspase activation.
- The pro-apoptotic effects of IFN-γ and TNF-α on ESCs may modulate early embryo implantation.
