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Apoptosis and Differential Expression of Apoptosis-Related Proteins in Endometriotic Glandular and Stromal Cells

Ioannis M. Matalliotakis, MD,PhD

Maria Tzardi, MD,PhD

Yvoni G. Fragouli, MD,PhD

Neal G. Mahutte, MD

Departments of Obstetrics and Gynecology and Pathology, University of Crete, Heraklion, Greece, Department of Hygiene and Epidemiology, University of Athens, Athens, Greece; Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut

Aydin Arici, MD

Departments of Obstetrics and Gynecology and Pathology, University of Crete, Heraklion, Greece, Department of Hygiene and Epidemiology, University of Athens, Athens, Greece; Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut; aydin.arici{at}yale.edu

Objective: Apoptosis is an important regulator of eutopic endometrial function. Endometriosis, the growth of endometrial tissue outside the uterus, could result from increased cellular proliferation or decreased apoptosis in response to appropriate stimuli. The objective of this study was to evaluate the rate of apoptosis and the expression of apoptosis-related Bcl-2 and Bax proteins in endometriotic tissues within the glandular and stromal compartments, according to the phase of the menstrual cycle and the stage of disease.

Methods: Ovarian endometriosis samples were evaluated in 75 women who had surgery at a university hospital. Apoptotic cells were detected with the use of the dUTP nick-end labeling (TUNEL) assay. Bcl-2 and Bax expression were assessed by immunohistochemical techniques.

Results: The percentage of apoptotic cells was significantly higher in endometriotic stormal cells (73.3%) compared with glandular cells (48%; P = .002). In contrast, the expression of the apoptosis-related proteins Bcl-2 and Bax was significantly lower in the endometriotic stroma (17.3% for both) than in the glandular epithelium (38.6% and 41.3%, respectively; P < .004). No significant menstrual cycle phase-dependent changes or endometriosis stage-related changes were observed in TUNEL, Bcl-2, or Bax positivity within ovarian endometriotic tissues.

Conclusion: Apoptosis occurs in ovarian endometriots lesions at significantly higher levels in the stroma than the glandular epithelium. However, Bcl-2 and Bax proteins are distributed preferentially in glandular epithelial cells. the apoptotic rate as well as Bcl-2 and Bax expression in ovarian endometriotic cells were not affected by the stage of endometriosis or the phase of thhe menstrual cycle.

Key Words: Apoptosis • Bcl-2 • Bax • endometriosis • glandular • stormal cells

Journal of the Society for Gynecologic Investigation, Vol. 11, No. 5, 318-322 (2004)
DOI: 10.1016/j.jsgi.2004.02.005


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