Reduction of apoptosis and proliferation in endometriosis

Abstract

Objective: To evaluate whether endometriosis could be related to an impaired balance between apoptosis and proliferation, two processes which could be modulated by hormonal status.Design: Immunohistochemical study.Setting: Academic research laboratory. Intervention(s):Endometriotic samples obtained from peritoneum of women aged 26-40 years who were undergoing laparoscopy for pain or infertility. Main Outcome Measure(s):Apoptotic cells were detected with the use of the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. The production of p53 and bcl-2, estrogen and Progesterone (P) receptors, and cellular proliferation were assessed by immunohistochemistry in eutopic and ectopic endometria from 30 patients with endometriosis throughout the menstrual cycle. Results were compared with those from normal endometria from 15 fertile patients. Result(s):Endometriotic lesions were characterized by reduced TUNEL and p53 stainings and by enhanced bcl-2 staining. No correlation between apoptosis and estrogen receptor or P receptor levels was found. A lower amount of steroid receptor was found in endometriotic tissues, without cyclic modulation, compared with the eutopic endometrium. Conclusion(s):Our results suggest that when endometrial tissue is located at ectopic locations, it differs from eutopic endometrium by its proliferation rate, steroid hormone levels, and markers of apoptosis. A reduced sensitivity of endometriotic cells to apoptosis could promote the dissemination and implantation of these cells to ectopic sites.

Deficiency of Immunophilin FKBP52 Promotes Endometriosis

“…These results in mice are in accord with previous findings of reduced PR expression in human endometriosis. 11,25,26 We also observed that FKBP52 levels were reduced in ectopic lesions of WT-WT samples with only a few stromal cells showing expression ( Figure 4B …”

“…In fact, the pattern of cell proliferation in ectopic lesions differs from estrogen-and P 4 -governed proliferation of eutopic endometria. 25,26 The proliferative status of mouse ectopic lesions due to FKBP52 deficiency was assessed by Ki-67 immunohistochemistry. For Ki-67 quantification, five high-powered fields per respective section were analyzed microscopically.…”

Role of iron overload-induced macrophage apoptosis in the pathogenesis of peritoneal endometriosis

“…Accumulated evidence indicates that decreased apoptosis of endometrial cells in a phase-dependent manner during the menstrual cycle may facilitate ectopic survival of implanted endometrial fragments (Dmowski et al 2001, Garcia-Velasco & Arici 2003. In healthy women, the endometrium that is refluxed into the peritoneum undergoes apoptosis called anoikis because of its failure to interact with the extracellular matrix required for the growth of ectopic endometrium (Béliard et al 2004). The resistance of endometrial cells to apoptosis and their increased sensitivity to proliferation is one of the proposed theories for the development of endometriosis (Harada et al 2004).…”

Analysis of p53 codon 72 gene polymorphism in Brazilian patients with endometriosis

“…Endometriosis is a pathologic condition that involves abnormal endometrial cell adhesion, growth, and proliferation in ectopic tissues, such as the ovary and the peritoneal surface (Béliard et al, 2004). Studies of p53 codon 72 polymorphism with respect to the incidence of endometriosis have been controversial.…”