Evaluation of Toll-like receptor 3 (TLR3) signaling pathway genes and its genetic polymorphisms in ectopic and eutopic endometrium of women with endometriosis

Abstract

Objective: Toll-like receptors (TLRs, as members of the innate immune system) are expressed in the human endometrium and their aberrant regulation and expression are involved in the pathogenesis of endometrial diseases. This study is aimed at evaluation of TLR3 signaling pathway genes and its genetic changes in endometriosis patients.

Materials and methods: Blood samples were collected from 83 endometriosis patients and 93 healthy fertile women and PCR was performed in blood-derived DNA for detection of SNP of TLR3. Also, ectopic (EC) and eutopic (EU) endometrial biopsies were obtained from endometriosis patients (n = 20), as well as endometrium from healthy women (n = 16, CE). 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). Also, serum protein levels of TLR3, IFN-β, IL-6 and IL-8 were determined using ELISA.

Results: The mRNA expression levels 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. SNPs frequency (rs3775291 and rs3775290) was not significantly different between patients and controls. Serum protein levels of TLR3, IFN-β, IL-6 and IL-8 were significantly increased in endometriosis patients.

Conclusion: Significant changes were observed in the expression of IL-6 and IL-8 cytokines and other genes in TLR3 cascade in diseased EU, demonstrating that EU similarly to EC is in an intensive inflammatory state. These fundamental alterations in the concept of immune response in EU may lead to its activation, escapes from apoptosis, and displaced implantation of the endometrium.

Keywords: Endometriosis; Polymorphism; SNPs; Toll-Like Receptor 3.