Differential proteome profiling of eutopic endometrium from women with endometriosis to understand etiology of endometriosis.

The identification of molecular differences in the endometrium of women with endometriosis is an important step toward understanding the pathogenesis of this condition and for developing novel strategies for the treatment of associated infertility and pain. In this study, we investigated protein expression analysis of eutopic endometrium from women with and without endometriosis. The proteomic analysis revealed molecular dysregulation of more than 70 proteins in the proliferative phase of eutopic endometrium in stage IV and secretory phase of stage II, III and IV endometriosis. Using mass spectrometry, 48 proteins spots which were consistently differentially expressed from stage II to IV endometriosis were identified. The differentially expressed proteins include structural proteins, proteins involved in stress response, protein-folding and protein-turnover, immunity, energy production, signal transduction, RNA biogenesis, protein biosynthesis, and nuclear proteins. Immunoblot and immunohistochemical analyses confirmed the observed changes in eight representative proteins. The present study provides identification of new players that have a potential role in the initiation and progression of endometriosis and also sets a framework for further investigations on mechanisms underlying the pathogenesis of endometriosis.

Susceptibility Risk Alleles of -238G/A, -308G/A and -1031T/C Promoter Polymorphisms of TNF-α Gene to Uterine Leiomyomas.

BACKGROUND: Uterine Leiomyomas (UL) are non-cancerous single celled mass of uterine smooth muscles distinguished by presence of large amounts of collagen, fibronectin and proteoglycans. Tumor necrosis factor-α (TNF-α), an inflammation inducing cytokine, plays a major role in various disorders of the immune system; is involved in tumor development and progression. It is proposed to study the influence of three functional promoter polymorphisms of TNF-α viz -238G/A, -308G/A and -1031T/C in the development and progression of UL. METHODOLOGY: Study included 146 individuals positive for uterine fibroids and 150 healthy individuals. Genomic DNA was isolated from white blood corpuscles and subjected to PCR-RFLP analysis and Allele Specific PCR (ARMS). The significance of the obtained data in controls and patients was estimated and computed by adopting appropriate statistical tools. RESULTS: In this study an association between TNF-α -1031T/C polymorphism and UL was reported. A significant association of the TC genotype (χ(2) - 14.34; p=0.0008) and the C allele (χ(2) - 5.898 p=0.015) with uterine leiomyomas was observed. Likewise odds risk estimates of 2.56 (95% CI 1.56-4.20, p=0.0007) revealed a significant association of TC genotype and C allele with uterine leiomyomas. CONCLUSIONS: "TC" genotype and "C" allele of rs1799964 (-1031T/C) is associated with higher risks to leiomyomas. The "C" allele of -1031T/C results in an increased expression TNF-α leading to smooth cell proliferation and tumor progression, hence, may be a relevant molecular marker in the identification and establishment of UL.

GSTM1, GSTT1 and CYP1A1 detoxification gene polymorphisms and their relationship with advanced stages of endometriosis in South Indian women.

OBJECTIVE(S): Studies on association between endometriosis and various phase I and phase II detoxification genes such as glutathione S-transferase M1 and theta 1 (GSTM1 and GSTT1) and cytochrome P450 (CYP1A1) have produced inconsistent results possibly because of ethnic differences. The present study was undertaken to investigate the frequency of the CYP1A1 (6235T>C) polymorphism and GSTM1, GSTT1 null mutations in a South Indian women's population with and without endometriosis. METHODS: The frequencies of variants were studied in 310 women with laparoscopically proven endometriosis (rAFS III=101; IV=209) and 215 women without endometriosis using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The GSTM1 null deletion showed significant association (P=0.028) with endometriosis. No significant difference was found in the frequencies of the GSTT1 null deletion in cases and controls. The frequencies of the variant CYP1A1 homozygous and heterozygous alleles in the cases were 9% and 44.2% against 14.4% and 42.3% in the controls. Further, we observed a considerable difference in the GSTM1 null deletion frequency in this population when compared with other populations of the world. CONCLUSIONS: We observed an association between endometriosis and the GSTM1 null deletion, but not with GSTT1 null deletions or the CYP1A1 MspI polymorphism in South Indian women.