Published online before print June 4, 2009

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(American Journal of Pathology. 2009;175:215-224.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.080966

Disrupted Cell Cycle Control in Cultured Endometrial Cells from Patients with Endometriosis Harboring the Progesterone Receptor Polymorphism PROGINS

Paulo D'Amora^*, Thiago Trovati Maciel, Rodrigo Tambellini, Marcelo A. Mori, João Bosco Pesquero, Helio Sato^*, Manoel João Batista Castello Girão^*, Ismael Dale Cotrim Guerreiro da Silva^* and Eduardo Schor^*

From the Gynecology Department,^* Molecular Gynecology and Proteomics Laboratory, Pelvic Pain and Endometriosis Unit; the Nephrology Division, Molecular and Cell Biology Laboratories, and the Department of Biophysics, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, Brasil

Presently, little is understood about how endometriosis is established or maintained, or how genetic factors can predispose women to the disease. Because of the crucial role that the progesterone receptor polymorphism PROGINS plays in predisposing women to the development of endometriosis, we hypothesized that this variant may influence critical steps during endometrial cell metabolism that are involved in the pathogenesis of endometriosis. Eutopic endometria were collected from three sources: women with endometriosis who had a single PROGINS allele (from the progesterone receptor gene); women with endometriosis who had the wild-type progesterone receptor allele; and women without endometriosis who had the wild-type allele. Cells prepared from the eutopic endometria of these women were stimulated with both estradiol and progesterone, and then examined for cell proliferation, viability, and apoptosis. The cells from women with endometriosis that carried the PROGINS allele demonstrated increased proliferation, greater viability, and decreased apoptosis following progesterone treatment. In general, these parameters were very different as compared with those of women with endometriosis but without the PROGINS allele and women in the control group. This result indicates there is a reduced level of progesterone responsiveness in women who carry the PROGINS polymorphism. Because progesterone responsiveness is known to be an important characteristic of women with endometriosis, these data support the contention that the PROGINS polymorphism enhances the endometriosis phenotype.