Alterations of Toll-Like Receptor 3 Related Genes in Endometriosis Patients

Background: Toll-like receptor 3 (TLR3), comprises a family of receptors through directly recognizing exogenous and en-dogenous ligands, plays the key role in realization of immune responses, and also involves in the processes of cell prolifera-tion, survival, apoptosis and tissue remodeling. Aberrant ex-pression of TLR3 and some its downstream genes involved in the pathogenesis of immunological diseases. Endometriosis, a common gynecologic disorder that is characterized by the ec-topic growth of endometrial tissue, has described as a genetic, hormonal and also immune disease. This study aimed at evalu-ation of TLR3 and some signaling pathway genes in eutopic en-dometrium (EU) and ectopic (EC) as well as serum parameters in women with endometriosis.Material and Methods: Twenty endometriosis lesions from EC and EU biopsies were obtained from endometriosis women,as well as endometrium from healthy women (n=16, as control group, CE) in the proliferative phase of menstrual cycle (days 5 to 14). Q-PCR was performed for determination of mRNA expression level of TLR3 signaling pathway genes (TLR3, TICAM, NF-kB1A, CXCL10, IRF3, IFN-B1, IL-6 and IL-8 genes) in tissue samples. Also, serum protein levels of TLR3, IFN-β, IL-6 and IL-8 were determined by ELISA Assay.Results: MRNA gene expression of TLR3, NF-kB1A, IFN-B1, IRF3, TICAM1, IL-6 and IL-8 were significantly higher in EU compared to ectopic ones and also compared to CE (P<0.05 or P<0.01). There was no significant difference in CXCL10 expression between EU vs. CE whereas its mRNA expression was significantly higher in EU than ectopic ones. Serum pro-tein levels of TLR3, IFN-β, IL-6 and IL-8 were significantly increased in patients with endometriosis in comparison to the control (P<0.05).Conclusion: In this study, moreover to elevation of IL-6 and IL-8 cytokines, significant and clear changes was observed in the mRNA expression of other genes in TLR3 cascade in dis-eased eutopic endometrium, demonstrating that EU similarly to EC was in an intensive inflammatory state. Interestingly, the results showed that expression of aforementioned genes have significant difference between ectopic and eutopic endome-trium of endometriosis patients, suggesting that fundamental alterations in the concept of immune response in eutopic endo-metrium may lead to its activation and escapes from apoptosis. These changes maybe have potential contribution to misplaced implantation of endometrium, and then ectopic tissues become stable to a certain degree from the immunological point of view.

Keywords:

Endometriosis , TLR3 , Toll-Like Receptor 3 , Signal-ing Pathway , Expression