The effect of antiprogestin on integrin expression in human endometrium: an immunohistochemical study

Integrins are cell surface receptors for the extracellular matrix and connect extracellular cell adhesion proteins to cytoskeletal components. Several investigators have recently described the expression of different integrins in the human endometrium as markers of receptivity. In the present study we investigated the effect of various doses of the antiprogestin mifepristone on the endometrial expression of integrins during the implantation phase. Endometrial biopsies from healthy fertile women were obtained in the midluteal phase. The study included one control and one, two or three treatment cycles. In treatment cycles either 2.5 (n = 9) or 5 mg (n = 5) of mifepristone was administered once weekly, 0.5 mg daily (n = 5), or 200 mg as a single dose administered on day 2 after the luteinizing hormone surge (day LH + 2; n = 8). By using polyclonal antibodies against integrin alpha(v)beta3, subunit beta3 and subunit alpha4 we found reduced immunostaining for alpha4 and beta3 subunit in glandular epithelium after treatment with mifepristone while alpha(v)beta3, expression appeared to be unaffected. No differences between treatment groups were noted. This study demonstrates that treatment with mifepristone interferes with integrin distribution during the implantation window. This may imply that the contraceptive effect of mifepristone is primarily due to impaired endometrial receptivity. However, since no effect was shown on the distribution of the vitronectin receptor, this integrin might be regulated differently by other factors such as cytokines.