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PATTERN-RECOGNITION RECEPTORS, ACTIVATED BY BACTERIAL LIGANDS, IN PATHOGENESIS OF MISSED AND SPONTANEOUS ABORTIONS
Abstract
Background. Immune causes of miscarriages are not well known. Toll-like receptors (TLR) are receptors of innate immunity, situated on innate immunity cells, including epithelial cells, and capable to recognize structures of pathogens (bacteria, viruses, fungi and protozoa) and activate immune response. Toll-like receptors, recognizing bacterial structures, are membrane receptors, which through MyD88-dependent pathway activate synthesis of proinflammatory cytokines. TLR1, TLR2 and TLR6 recognize lipopeptides of Gram-positive bacteria and fungi. TLR4 recognizes lipopolysaccharides of Gram-negative bacteria, TLR5 – bacterial flagellin. For TLR10 ligand is unknown, but it is suggested, that it has bacterial nature. The aim of research was to estimate expression of TLR1, TLR2, TLR4, TLR5, TLR6 and TLR10 in endometrium of patients with spontaneous and missed abortions. Methods. 22 patients with missed abortions, 22 patients with spontaneous abortions and 57 patients with progressive pregnancy (control group, admitted for medical abortion) were examined. Gestational age of termination of pregnancy in all cases was 6-10 weeks. Patients with endocrine diseases, severe extragenital disorders and antiphospholipid syndrome were excluded from research. Endometrial tissue was taken by uterine abrasion. Expression of mRNA of TLR1, TLR2, TLR4, TLR5, TLR6, TLR10 in endometrium was performed by quantitative PCR. Statistical analysis was done by Mann-Whitney test using Statistica 5,0 (Statsoft, USA). Results. In endometrium of patients with spontaneous miscarriages expression of mRNA of TLR6 was significantly lower (0,074 (0,013; 0,129)), than in the control group (7,14 (0,15; 10,30)) (p=0,0002). Expression of mRNA of TLR1, TLR2, TLR4, TLR5 and TLR10 has no significant difference compared with control group. In patients with missed abortion mRNA expression of TLR6 was also significantly lower (0,026 (0,0003; 0,128)), than in the control group (p=0,0001). Expression in endometrium of patients with missed abortion TLR1, TLR2, TLR4, TLR5 and TLR10 mRNA also has no significant difference compared with control group. Expression of mRNA of TLR5 was 3 times higher in patients with missed abortions (0,00028 (0,00011; 0,00079) compared with patients with spontaneous abortions 0,000098 (0,000026; 0,00033), p=0,04). No difference in expression of other TLRs was observed between group with missed abortions and group with spontaneous abortions. Conclusions. Sufficient decrease of TLR6 mRNA expression in endometrium is typical for spontaneous and missed abortions. Expression of TLR5 mRNA was higher in patients with missed abortions compared with women with spontaneous abortions. These data can be useful for future therapy development.
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