TNF system in eutopic endometrium from women with endometriosis

The role of the tumor necrosis factor (TNF) system in endometriosis is not completely clear and therefore was the focus of this study. In eutopic endometria obtained from women with (n = 41) and without (controls; n = 34) endometriosis during laparoscopy, the subcellular location and the percentages for TNF, TNFR1, TNFR2 and CD45 positive-cells were determined (immunohistochemistry); the protein concentration (ELISA) of the soluble receptors (sTNFR1 and sTNFR2) were measured in 4h-explants culture media and the TNF concentration was performed in ex vivo endometrial homogenates. The TNF, TNFR1 and TNFR2 mRNAs were analyzed by real-time PCR. In control endometria, TNF, TNFR1 and sTNFR1 proteins increased during the late secretory phase. In endometriosis endometria, the protein highest level of TNFR1 was reached during the early and the mid secretory phases and of sTNFR1 concentration during the proliferative phase; however, during the late secretory phase, both TNFR1 and sTNFR1 protein levels were reduced compared to the control endometria (p < 0.05). TNFR2 was scarcely immunodetected in some CD45-positive stromal cells. The TNFand CD45-positive cell percentages, the TNF and sTNFR2 concentrations, and TNF and TNFR2 mRNAs were similar in control and endometriosis endometria. Although TNFR1 mRNA was highly expressed, no significant differences were found between control and endometriosis endometria. In summary, this study establishes that TNF and TNFR1 protein expressions and the sTNFR concentrations in eutopic endometria from women with and without endometriosis are dependent on the menstrual cycle. The differences on the TNFR1 and sTNFR1 protein pattern between both groups, mainly during the mid and late secretory phases may play a role in the lower implantation rates observed in women with endometriosis, and also could be related to the altered cell death, which favor the augmented cell viability facilitating the characteristic endometrial implantation and growth outside the uterus in this disease.