Disrupted cell cycle control in cultured endometrial cells from patients with endometriosis harboring the progesterone receptor polymorphism PROGINS.
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.
D'Amora
Paulo
P
Pelvic Pain and Endometriosis Unit, Gynecology Department, Molecular Gynecology and Proteomics Laboratory, Universidade Federal de São Paulo - Escola Paulista de Medicina, São Paulo, Brasil. paulo.toco@epm.br
Maciel
Thiago Trovati
TT
Tambellini
Rodrigo
R
Mori
Marcelo A
MA
Pesquero
João Bosco
JB
Sato
Helio
H
Girão
Manoel João Batista Castello
MJ
Guerreiro da Silva
Ismael Dale Cotrim
ID
Schor
Eduardo
E
D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D004715:Endometriosis / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D006801:Humans; D011110:Polymorphism, Genetic; D011374:Progesterone / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D011372:Progestins; D011980:Receptors, Progesterone; D011374:Progesterone