title: Low-dose mifepristone increases uterine natural killer cell cytotoxicity and perforin expression during the receptive phase.
abstract: OBJECTIVE
  To investigate the immunologic mechanism by which low-dose mifepristone serves as an anti-implantation contraceptive drug.
  
  
  METHODS
  In vitro study.
  
  
  METHODS
  University hospital and research laboratory.
  
  
  METHODS
  Fifteen normally cycling patients at the "window of implantation."
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
authors: Feng
authors: F
authors: Zhou
authors: Xiu-Ying
authors: XY
authors: Chen
authors: Ya-Ling
authors: YL
authors: Zhuang
authors: Yue-Zhou
authors: YZ
authors: Chen
authors: Li-Li
authors: LL
authors: Huang
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D003280:Contraceptives, Oral, Synthetic / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation / Q000276:immunology; D004717:Endometrium / Q000187:drug effects / Q000276:immunology; D005260:Female; D005298:Fertility / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008597:Menstrual Cycle / Q000276:immunology; D015735:Mifepristone / Q000494:pharmacology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D003280:Contraceptives, Oral, Synthetic; C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D015735:Mifepristone