Effects of mifepristone on the human endometrium and the fallopian tube during the luteal phase

Abstract

Mifepristone given postovulatory has been shown effective for contraception, but the precise mechanism of action is still poorly understood. A better understanding of the mechanisms of action of mifepristone, when used for contraception, is important for further development and optimizing the regimen of use.

To study the effects of mifepristone during the luteal phase, a single dose of 200mg mifepristone was administered on day LH+2. Endometrial biopsies were obtained on day LH+6 to LH+8 (the expected time for endometrial receptivity and implantation) and the fallopian tube on day LH+4 to LH+6 (approximately the time when the embryo is still in the fallopian tube). Immunohistochemistry, RT-PCR and Western blot were used for analysis of the endometrium and the fallopian tube samples.

After treatment with mifepristone, progesterone receptor isoform B (PR-B) concentrations increased in glandular cells of the endometrium and in epithelial and stromal cells in the fallopian tube. In the endometrium endothelial nitric oxide synthase (eNOS) expression was attenuated in the glandular epithelium, in contrast to endothelial eNOS, which was not changed. The expression of insulin-like growth factor binding protein-1 (IGFBP-1) was significantly increased in the glandular epithelial cells. The staining intensity of heparin-binding epidermal growth factor-like growth factor (HB-EGF) was not affected by mifepristone.

Treatment with mifepristone increased the immunostaining of HB-EGF receptor HER1 in the epithelium and the stroma in the endometrium, while the opposite was seen in the luminal epithelium of the fallopian tube. The immunostaining of HB-EGF receptor HER4 increased in the epithelial cells of the endometrium, while a decrease was seen in the stroma of the fallopian tube.

In conclusion these results indicate that mifepristone administered immediately after ovulation has pronounced effects on the endometrium at the expected time of endometrial receptivity. These changes may contribute to cause defective endometrial receptivity and altered intraluminal milieu. The effect on the fallopian tube may also be of importance for the contraceptive effect of mifepristone.