Endometrial integrins and the establishment of uterine receptivity

Our understanding of the factors responsible for the initial interaction between maternal and embryonic epithelium leading to successful implantation remains incomplete. Temporal and spatial expression of specific endometrial peptides may contribute to the establishment of a period of uterine receptivity, whereby the endometrium becomes hospitable to the implanting blastocyst. The failure to establish receptivity may account for a significant number of cases of infertility in the female, especially affecting women with luteal phase deficiency, endometriosis, hydrosalpinges, recurrent pregnancy loss and unexplained infertility. Integrins are a family of cell adhesion molecules that have now been largely accepted as markers of uterine receptivity. Their pattern of expression during the menstrual cycle suggests that integrins may also provide a means to study the factors that regulate the establishment of uterine receptivity in general. The vitronectin receptor is an alpha-v-beta-3 integrin that appears during the opening of the putative window of implantation. Its expression appears to be associated with the down-regulation of epithelial oestrogen and progesterone receptors (PR). We postulate that the selective loss of PR on endometrial epithelium is critical to the establishment of uterine receptivity and allows the emergence of paracrine influence by underlying stroma through specific growth factors. Disruption of the normal pattern of integrins found in certain infertility states may also reflect a shift in the paracrine milieu, possibly due to the influence of inflammatory cytokines associated with endometriosis or tubal disease. Understanding what regulates and dysregulates endometrial integrins may lead to better treatment and diagnostic strategies for infertility patients as well as novel approaches to contraception.