The role of oxidative stress in the pathogenesis and function of endometriosis (#145)
Pathophysiology of endometriosis (affecting 5–15% of women of reproductive age) remains elusive1,2 . We applied proteomic approaches to investigate potential differences in the three main lesion phenotypes of endometriosis (peritoneal, ovarian and deep-infiltrating). We aimed to investigate the endometrial proteome from women with the three phenotypes, compared to controls, to identify key molecular pathways involved in pathogenesis and function, relevant to mechanisms of lesion development.
Materials & Methods
2D fluorescence difference gel electrophoresis was performed on proteins extracted from proliferative and secretory phase endometrium obtained from women undergoing laparoscopy (subgrouped into peritoneal, ovarian, deep-infiltrating endometriosis and controls, n=6 in each group). Resulting gel images were analysed to detect differential protein abundance levels (Progenesis SameSpot, NonLinear Dynamics). Proteins of interest were identified using MALDI-TOF mass spectrometry (Voyager, AB Sciex, Australia) and MASCOT (Matrix Science, UK).
Results & Conclusions
Progenesis demonstrated that 18 spots (from 295) were differentially abundant (>1.5 fold change) in endometrium of women with endometriosis compared to controls (p<0.05). Beta-actin, haemoglobin subunit beta (Hb-β), peroxiredoxin-2 (PRDX-2), and L-lactate dehydrogenase B chain (LDHB) and their isoforms, were identified. Endometrial PRDX-2 (p=0.031) and LDHB (p=0.011) were significantly more abundant in women with peritoneal endometriosis compared to women with ovarian or deep-infiltrating disease.
This study provides novel evidence of subtle changes in molecular profile of endometrium in women with different endometriosis lesion phenotypes, further supporting the hypothesis that endometriosis is an endometrial disease. Oxidative stress has been suggested to play a role in endometriosis pathogenesis. Hence, increased endometrial expression of PRDX-2 (an antioxidant enzyme), LDHB (catalytic enzyme in glycolysis metabolism) and Hb-β in women with peritoneal disease may contribute to an inflammatory process, viability and persistence of refluxed endometrial cells, resistant to apoptosis, evading immunological responses and permitting survival and implantation at ectopic sites.
- M Ulukus et al. The role of the endometrium in endometriosis 13(7):467-76; J Soc Gynecol Investig. 2006.
- M Al-Jefout et al. The microanatomy and function of the eutopic endometrium in women with endometriosis 4(1):61-79; Expert Rev Obstet Gynecol. 2009.