The molecular events that predispose one women to endometriosis and infertility while sparing another remains poorly understood. A new class of cell adhesion molecules, known as integrins, appear to play major roles in the functioning of the endometrium and in the normal behavior of these and other cells in the body. This class of glycoproteins has been shown to be important in the invasive and metastatic potential of neoplasms, and thus may be involved in the behavior of endometrial cells in patients with endometriosis. Further, we present evidence to suggest that certain integrins participate in the implantation process, and that their presence may be critical to the establishment of pregnancy and normal cycle fecundity. Patients with endometriosis display differences in the complement of integrins and we hypothesize the following: 1) the loss of specific integrins may predispose certain women to the establishment of endometriosis; 2) the abnormal environment of the endometrial implant results in loss of normal integrin and extracellular matrix expression, and this difference explains the discordance seen between normal and ectopic endometrium; and 3) disruption in the critical timing of certain integrins in the eutopic endometrium occurs specifically in women with endometriosis, and this disruption results in the infertility some women with this disorder experience. We will immunohistochemistry and in situ hybridization to establish what the normal pattern of integrin expression is in normal women. Integrins will then be similarly and extensively studied in women with endometriosis. Defects in the timing and expression of one integrin, the vitronectin receptor, on the lining of the endometrium will be studied as a marker of uterine receptivity in these patients and compared to normal controls. Finally, an in vitro model of invasion will be established to study differences between the behavior of endometrium from women with and without this disease. By characterizing this class of molecules in endometriosis and in the endometrium of women with and without this disorder, we hope to establish a better understanding of the etiology and pathogenesis of endometriosis, and we believe this will lead to better treatment regimes in these patients.
Showing the most recent 10 out of 28 publications
