Background: Toll-like receptors play a crucial role in the immunological interaction between the spermatozoa and fallopian tube and contribute to the ovulation, sperm capacitation, fertilization, and pregnancy. Objectives: To investigate the expression of toll-like receptors and their adaptor molecules and cytokines under the effect of spermatozoa with high DNA fragmentation (high DF) in human fallopian tube cell line (OE-E6/E7) and compare to those in normal spermatozoa. Materials and methods: Fresh semen samples were obtained from 10 unexplained infertile males with high DF (more than 20%) and from 10 healthy donors with a DF less than 3%. After sperm preparation, samples were co-cultured with OE-E6/E7. Toll-like receptors, myeloid differentiation factor 88 (MyD88), TIR domain-containing adapter protein (TIRAP), TIR domain-containing adapter-inducing IFN-b (TRIF), TRIF-related adapter molecule as well as IL-6, IL-8, IFN-b, and TNFa mRNA expression were evaluated by quantitative real-time PCR. Protein levels of these cytokines and chemokines were measured using ELISA method. Results: TLR 1-6 mRNA expression in OE-E6/E7 was significantly higher under the effect of spermatozoa with high DF compared to the spermatozoa with low DF. Furthermore, significantly increased mRNA expression of MyD88, TIRAP, and TRIF was observed in the high DF group compared to the low DF group, except TRIF-related adapter molecule. Moreover, the expression of IL-6 and IL-8 in the high DF group was significantly higher than low DF group, although there was no significant difference in IFN-b and TNFa expression between the groups. Discussion and conclusion: Damage-associated molecular patterns from DNA damage activate TLR signaling pathway in human fallopian tubes and result in the upregulation of inflammatory cytokines and chemokines. This situation may provide pathologic environment for capacitation, fertilization, embryo development, and implantation in female reproductive tract and can be one of the mechanisms of infertility in men with high DF.

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ObjectiveThe fallopian tubes play a critical role in the early events of fertilization. The rapid innate immune defense is an important part of the fallopian tubes. Toll-like receptor 3 (TLR3), as a part of the innate immune system, plays an important role in detecting viral infections. In this basic and experimental study, the effect of sex hormones on the function of TLR3 in the OE-E6/E7 cell line was investigated.MethodsThe functionality of TLR3 in this cell line was evaluated by cytokine measurements (interleukin [IL]-6 and IL-1b) and the effects of sex hormones on TLR3 were tested by an enzyme-linked immunosorbent assay kit. Additionally, TLR3 small interfering RNA (siRNA) and a TLR3 function-blocking antibody were used to confirm our findings.ResultsThe production of IL-6 significantly increased in the presence of polyinosinic-polycytidylic acid (poly(I:C)) as the TLR3 ligand. Using a TLR3-siRNA-ransfected OE-E6/E7 cell line and function-blocking antibody confirmed that cytokine production was due to TLR3. In addition, 17-β estradiol and progesterone suppressed the production of IL-6 in the presence and absence of poly(I:C).ConclusionThese results imply that sex hormones exerted a suppressive effect on the function of TLR3 in the fallopian tube cell line when different concentrations of sex hormones were present. The current results also suggest that estrogen receptor beta and nuclear progesterone receptor B are likely to mediate the hormonal regulation of TLR3, as these two receptors are the main estrogen and progesterone receptors in OE-E6/E7 cell line.

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