Effects of anti-endometriotic therapies on Fas-mediated endometrial epithelial apoptosis

Decreased numbers of eutopic endometrial apoptotic cells have been reported in endometriotic patients, indicating the possibility of anti-apoptotic effects of their sera. Recently, we reported that the sera from endometriotic patients enhance endometrial stromal cell proliferation and viability, and that Keishi-bukuryo-gan therapy, an anti-endometriotic Japanese herbal medicine, reduces anti-apoptotic activities in the sera. In this study, we therefore examined the effects of sera from 7 endometriotic patients on cell proliferation and Fas-mediated apoptosis of the human endometrial epithelial cell line HHUA, which has a normal karyotype and functional estrogen and progesterone receptors. Cell proliferation was not affected by any of the sera examined, including sera from healthy women. The sera of 6 out of 7 endometriotic patients and sera from 2 healthy women significantly inhibited Fas-mediated apoptosis in the cells. Moreover, anti-apoptotic activities in the sera of endometriotic patients on Fas-mediated apoptosis were not affected by gonadotropin-releasing hormone agonist (GnRHa) therapy within 4 weeks or Keishi-bukuryo-gan therapy within 12 weeks. Considering these results, we suggest that the surviving factor(s) against Fas-mediated endometrial epithelial cell apoptosis in human sera can be found in endometriotic and non-endometriotic women, and that decreased eutopic endometrial epithelial apoptosis in endometriotic patients might be caused by the secondary effects of endometrial stromal cell growth and surviving factor(s) in sera of the patients, not by direct serum effects on the epithelium.