Low-dose mifepristone increases uterine natural killer cell cytotoxicity and perforin expression during the receptive phase

Objective: To investigate the immunologic mechanism by which low-dose mifepristone serves as an anti-implantation contraceptive drug. Design: In vitro study. Setting: University hospital and research laboratory. Patient(s): Fifteen normally cycling patients at the window of implantation. Intervention(s): A human endometrial explant system was used to study the effects of low-dose mifepristone (65 and 200 nmol/L) on uterine natural killer (uNK) cells. Endometrial samples were treated with different concentrations of mifepristone. Main Outcome Measure(s): The cytotoxicity of uNK cells to K562 target cells and the expression of perforin (PFN) by uNK cells were examined using a methyl thiazolyl tetrazolium (MTT) assay and double immunohistochemistry, respectively. Result(s): Both uNK cell cytotoxicity and expression of PFN were increased after treatment with 65 or 200 nmol/L mifepristone, and these effects were dose-dependent. Conclusion(s): Mifepristone may negatively regulate implantation by increasing the cytotoxicity of uNK cells, and this increased cytotoxicity may result from increased PFN expression. These findings provide further evidence to support the potential contraceptive activity of low-dose mifepristone. (Fertil Steril (R) 2011;96:649-53. (C)2011 by American Society for Reproductive Medicine.)