The effect of mifepristone on apoptosis and caspase-3 activation in human ovarian luteinized granulosa cells

Objective: To investigate the effect of mifepristone, an oral contraceptive, on apoptosis in human ovarian luteinized granulosa cells. Study design: Human ovarian luteinized granulosa cells were treated in vitro with 1.25, 2.5, 5.0, 10.0, or 20.0 mu M of mifepristone. Nuclear morphology, apoptosis ratio, and level of caspase-3 expression were determined with immunofluorescence microscopy, the terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay, and flow cytometry. Results: We found that mifepristone-treated cells contained single condensed chromatin with multiple nuclear fragments, which is morphologic evidence of apoptosis. A significant difference was observed in the TUNEL assay between mifepristone-treated cells and control cells (P < 0.05). Consistent with the results of the TUNEL assay, the fluorescence intensity of caspase-3 in drug-treated cells was also significantly different (P < 0.05) from control cells; specifically, the difference between cells treated with different doses of drugs was much smaller and negligible. Conclusion: From these results, we propose that mifepristone induces human ovarian luteinized granulosa cells to undergo apoptosis by activating caspase-3. (C) 2008 Elsevier Ireland Ltd. All rights reserved.