Low-dose mifepristone increases uterine expression of aquaporin 1/aquaporin 2 at the time of implantation.

ABSTRACT

BACKGROUND: The aim of this study was to investigate the mechanism by which low-dose mifepristone serves as an antiimplantation contraceptive drug. A human endometrial explant system was used to study the effects of low-dose mifepristone (65 nmol/L and 200 nmol/L) on expression of the water channel family aquaporins, aquaporin-1 and aquaporin-2 (AQP1/AQP2), at the time of implantation. STUDY DESIGN: Endometrial samples from 17 normally cycling patients at the "window of implantation" were treated with different concentrations of mifepristone. The protein and mRNA expression of AQP1/AQP2 in the endometrium was examined using immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. RESULTS: The IHC and RT-PCR analyses demonstrated that expression of AQP1/AQP2 was increased by mifepristone in a dose-dependent manner, with the highest AQP1/AQP2 expression levels detected in subjects treated with 200-nmol/L mifepristone. CONCLUSION: Low-dose mifepristone may negatively regulate implantation by increasing AQP1/AQP2 protein and mRNA expression. The findings from this study provide further evidence to support the potential contraceptive activity of low-dose mifepristone.