Modeling endometriosis

Abstract

Modeling the early endometriotic lesion is required for the study of endometriosis because the initial attachment of endometrial cells to peritoneal mesothelial cells cannot be observed in vivo. The complexity of this disease leaves many questions yet to be answered. Modeling the early endometriotic lesion is required for the study of endometriosis because the initial attachment of endometrial cells to peritoneal mesothelial cells cannot be observed in vivo. The complexity of this disease leaves many questions yet to be answered. We appreciate the insightful comments by Osteen et al. (1Osteen K.G. Bruner-Tran K.L. Eisenberg E. Endometrial biology and the etiology of endometriosis.Fertil Steril. 2005; 84: 33-34Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar), Sharp-Timms (2Sharpe-Timms K.L. Defining endometrial cells the need for improved identification at ectopic sites and characterization in eutopic sites for developing novel methods of management for endometriosis.Fertil Steril. 2005; 84: 35-37Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar), and Evers et al. (3Evers J.L.H. Gerard A. Dunselman G.A.J. Groothius P. Now you see them, now you don’t.Fertil Steril. 2005; 84: 31-32Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar). Their discussions emphasize the range and complexity of issues regarding the initial attachment of endometrial cells to peritoneal mesothelial cells in the early endometriotic lesion. These recognized investigators raise important issues regarding the role of steroids, cytokines and growth factors; endometrial cell type (stromal vs. epithelial), endometrial stage (menstrual, proliferative, or secretory), and endometrial source (women with or without endometriosis) in the study of endometriosis. These issues are valid and require further study. However, because the initial attachment of endometrial cells to peritoneal mesothelial cells cannot be observed in vivo, an in vitro model is the only way to assess the molecular and cellular mechanisms involved in the initial development of an endometriotic lesion. Previous work in our laboratory has focused on the genesis of the early endometriotic lesion. Our studies suggest that this process can be divided into three crucial events: [1] attachment of endometrial cells to peritoneal mesothelial cells, [2] transmesothelial invasion, and [3] persistence and proliferation in the submesothelial extracellular matrix. Our article in this issue (4Lucidi R.L. Witz C.A. Chrisco M. Binkley P.A. Shain S.A. Schenken R.S. A novel in vitro model of the early endometriotic lesion demonstrates that attachment of endometrial cells to mesothelial cells is dependent on the source of endometrial cells.Fertil Steril. 2005; 84: 16-21Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar) describes one model that facilitates the study of the first step in the genesis of the endometriotic lesion, namely endometrial cell-mesothelial cell attachment. Future research using this model will compare attachment of endometrial cells from women with and without endometriosis and evaluate the roles of hormones, cytokines, and growth factors. Differences of endometrial cell attachment to mesothelial cells might explain why some women develop endometriosis and others do not. We believe our study is a sound foundation from which to commence further research. We agree that it is not likely that single endometrial cells attach to mesothelial cells and form endometriotic lesions. This is not the thesis of our work. Our study identifies endometrial cells as the source of variation in initial attachment of endometrial cells to mesothelial cells. The results of our study focus future research on the differences in endometrial cell biology (rather than mesothelial cell biology) that are involved with the development of endometriosis. We fully recognize that attachment is only the first step in the genesis of endometriotic lesions. The rates of transmesothelial invasion and growth in the submesothelial extracellular matrix might also differ in patients with and without endometriosis. This is the focus of ongoing investigations in our laboratory.