Effect of mifepristone on the expression of cytokines in the human Fallopian tube.
Cytokines are believed to play a critical role as mediators between the oviduct and the developing embryo. A synchronous development of embryo and endometrium is essential to successful implantation. It seems to be beneficial for embryo development to rest for some time in the Fallopian tube. Expression of cytokines in the human Fallopian tube and the effect of mifepristone were investigated. Fourteen women with regular menstrual cycles and proven fertility, admitted to the hospital for tubal ligation, were randomly allocated to control or treatment groups. Mifepristone 200 mg was given on day LH+2. Surgery was performed on day LH+3 to LH+5. Biopsies were obtained from the ampullar and isthmic regions of the tubes. Expression of interleukin 8 (IL-8), tumour necrosis factor alpha (TNFalpha), transforming growth factor beta (TGFbeta) and leukaemia inhibitory factor (LIF) was analysed using immunohistochemistry. All cytokines except IL-8 showed the same staining intensity both in the ampullar and isthmic region, while IL-8 was more pronounced in the ampullar region in both epithelial and stromal cells. Exposure to mifepristone made the spatial difference in IL-8 disappear and increased the expression of TNFalpha in the epithelium of the isthmus, but had no effect on the expression of TGFbeta1 or LIF. Changes in cytokine expression in the Fallopian tube are likely to influence embryo development, which could contribute to the contraceptive effect of mifepristone.
Li
H Z
HZ
Department of Woman and Child Health, Division for Obstetrics and Gynaecology, Karolinska Institutet, S-171 76 Stockholm, Sweden.
Sun
X
X
Stavreus-Evers
A
A
Gemzell-Danielsson
K
K
D000328:Adult; D003280:Contraceptives, Oral, Synthetic / Q000378:metabolism / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D005187:Fallopian Tubes / Q000187:drug effects* / Q000276:immunology*; D005260:Female; D006727:Hormone Antagonists / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008875:Middle Aged; D015735:Mifepristone / Q000378:metabolism / Q000494:pharmacology*; D018121:Receptors, Cytokine / Q000378:metabolism; D053606:Receptors, OSM-LIF; D013246:Sterilization, Tubal; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D003280:Contraceptives, Oral, Synthetic; D016207:Cytokines; D006727:Hormone Antagonists; D016209:Interleukin-8; C507840:LIFR protein, human; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D015735:Mifepristone