INNATE IMMUNITY SIGNALING RECEPTORS IN THE INDUCTION OF APOPTOSIS IN EARLY MISCARRIAGE


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Abstract

Objective. To study the specific features of expression of toll-like receptor (TLR) 1-10 mRNA and the major apoptotic enzyme caspase-3a in patients with recurrent miscarriage at 6-10 weeks’ gestation. Subject and methods. The decidual tissue obtained when curetting the uterine in 57patients with spontaneous miscarriage at 6-10 weeks’ gestation (a study group) and in 57patients who had undergone medical abortion in the same gestational period (a control group) were examined. The expression of TLR 1-10 mRNA and caspase-3a in the endometrium was investigated using a quantitative polymerase chain reaction (PCR). Results. The patients with early miscarriage of infectious and inflammatory genesis showed an increased endometrial expression of TLR3, the ligand of which was viral double-stranded RNA. Those with spontaneous miscarriage were noted to have a decrease in TLR6 expression, which was strongly correlated with the endometrial activation of caspase-3a that is a major enzyme of irreversible apoptosis. There was no correlation between the expression of caspase and other TLRs. The expression of TLR6 had a positive moderate correlation with the number of births (R = 0.32; p = 0.03) and a weak negative correlation with the number of spontaneous miscarriages (R = -0.29; p = 0.002) in the history. Conclusion. Thus, the normal expression of TLR6 may play a protective role in the endometrium, interfering with miscarriages due to the prevention of apoptosis.

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About the authors

Olga Petrovna Lebedeva

Belgorod State National Research University

Email: safonova2@yandex.ru
Ph.D. Candidate, associate professor of the Department of Obstetrics and Gynecology Belgorod 308015, Pobedy str. 85, Russia

Olesya Nikolaevna Ivashova

Belgorod State National Research University

Email: pachomw@yandex.ru
postgraduate student of the Department of Obstetrics and Gynaecology Belgorod 308015, Pobedy str. 85, Russia

Natalia Yurevna Starceva

Belgorod State National Research University

Email: ivashovao2@yandex.ru
postgraduate student of the Department of Obstetrics and Gynaecology Belgorod 308015, Pobedy str. 85, Russia

Sergey Petrovich Pakhomov

Belgorod State National Research University

Email: starceva_nataliya@mail.ru
PhD Doctor, Professor, Head of the Department of Obstetrics and Gynaecology Belgorod 308015, Pobedy str. 85, Russia

Mikhail Ivanovish Churnosov

Belgorod State National Research University

Email: churnosov@bsu.edu.ru
PhD Doctor, Professor, Head of the Department of Medical Biology Belgorod 308015, Pobedy str. 85, Russia

References

  1. Тетруашвили Н.К., Агаджанова А.А. Программа обследования и предгестационной подготовки пациенток с привычным выкидышем. Акушерство и гинекология. 2012; 6: 87-91.
  2. Carp H.J.A. Recurrent pregnancy loss: causes, controversies and treatment. 2nd ed. CRC Press; 2014. 456 p.
  3. Радзинский В.Е., Димитрова В.И., Майскова И.Ю. Неразвивающаяся беременность. М.: ГЭОТАР-Медиа; 2009.
  4. Calleja-Agius J., Jauniaux E., Pizzey A.R., Muttukrishna S. Investigation of systemic inflammatory response in first trimester pregnancy failure. Hum. Reprod. 2012; 27(2): 349-57.
  5. Момот А.П., Тараненко И.А., Цывкина Л.П. Эволюция представлений о тромбофилии и ее роли в проблемах репродукции человека. Акушерство и гинекология. 2013; 2: 4-9.
  6. Ortel T.L. Antiphospholipid syndrome: laboratory testing and diagnostic strategies. Am. J. Hematol. 2012; 87(Suppl. 1): S75-81.
  7. Сухих Г.Т., Ванько Л.В. Иммунные факторы в этиологии и патогенезе осложнений беременности. Акушерство и гинекология. 2012; 1: 128-36.
  8. Bansal A.S., Bajardeen B., Shehata H., Thum M.Y. Recurrent miscarriage and autoimmunity. Expert Rev. Clin. Immunol. 2011; 7(1): 37-44.
  9. Kitaya K. Prevalence of chronic endometritis in recurrent miscarriages. Fertil. Steril. 2011; 95: 1156-8.
  10. Guenther S, Vrekoussis T., Heublein S., Bayer B., Anz D., Knabl J. et al. Decidual macrophages are significantly increased in spontaneous miscarriages and over-express FasL: a potential role for macrophages in trophoblast apoptosis. Int. J. Mol. Sci. 2012; 13(7): 9069-80.
  11. Arechavaleta-Velasco F., Gomez L., Ma Y., Zhao J., McGrath C.M., Sammel M.D. et al. Adverse reproductive outcomes in urban women with adeno-associated virus-2 infections in early pregnancy. Hum. Reprod. 2008; 23 (1): 29-36.
  12. Romero R., Espinoza J., Goncalves L.F., Kusanovic J.P., Friel L., Hassan S. The role of inflammation and infection in preterm birth. Semin. Reprod. Med. 2007; 25: 21-39.
  13. Rowe J.H., Ertelt J.M., Xin L., Way S.S. Regulatory T cells and the immune pathogenesis of prenatal infection. Reproduction. 2013; 146(6): R191-203.
  14. Medzhitov R., Janeway C.A. Jr. Decoding the patterns of self and nonself by the innate immune system. Science. 2002; 296(5566): 298-300.
  15. Freed E.O., Gale M. Jr. Antiviral innate immunity: editorial overview. J. Mol. Biol. 2014; 426(6): 1129-32.
  16. Shey M.S., Garrett N.J., McKinnon L.R., Passmore J. The role of dendritic cells in driving genital tract inflammation and HIV transmission risk: are there opportunities to intervene? Innate Immun. 2015; 21(1): 99-112.
  17. Horne A., Stock S., King A. Innate immunity and disorders of female reproductive tract. Reproduction. 2008; 135: 739-49.
  18. Wang H., Hirsch E. Bacterially-induced preterm labor and regulation of prostaglandin-metabolizing enzyme expression in mice: the role of toll-like receptor 4. Biol. Reprod. 2003; 69: 1957-63.
  19. Mulla M.J., Brosens J.J., Chamley L.W. Antiphospholipid antibodies induce a pro-inflammatory response in first trimester trophoblast via the TLR4/MyD88 pathway. Am. J. Reprod. Immunol. 2009; 62(2): 96-111.
  20. Rose J.A., Rabenold J.J., Parast M.M., Milstone D.S., Abrahams V.M., Riley J.K. Peptidoglycan induces necrosis and regulates cytokine production in murine trophoblast stem cells. Am. J. Reprod. Immunol. 2011; 66(3): 209-22.
  21. Bustin S.A., Benes V., Garson J.A., Hellemans J., Huggett J., Kubista M. et al. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin. Chem. 2009; 55(4): 611-22.
  22. Anzivino E., Fioriti D., Mischitelli M., Bellizzi A., Barucca V., Chiarini F., Pietropaolo V. Herpes simplex virus infection in pregnancy and in neonate: status of art of epidemiology, diagnosis, therapy and prevention. Virol. J. 2009; 6: 40. doi: 10.1186/1743-422X-6-40.
  23. Lin Y., Zeng Y., Di J., Zeng S. Murine CD200+ CK7+ trophoblasts in a poly (I:C) - induced embryo resorption model. Reproduction. 2005; 130: 529-37.
  24. Lin Y., Liang Z., Chen Y., Zeng Y. TLR3-involved modulation of pregnancy tolerance in double-stranded RNA-stimulated NOD/SCID mice. J. Immunol. 2006; 176: 4147-54.
  25. Nansen A., Thompsen A.R. Viral infection causes rapid sensitization to lipo- polysaccharide: central role of IFN-alpha beta. J. Immunol. 2002; 166: 982-8.
  26. Sun R., Zhang Y., Lu Q., Liu B., Jin M., Zhang W. et al. Toll-like receptor 3 (TLR3) induces apoptosis via death receptors and mitochondria by up-regulating the transactivating p63 isoform alpha (TAP63alpha). J. Biol. Chem. 2011; 286(18): 15918-28.
  27. Gavan T.M., Pavelic J. The exploitation of toll-like receptor 3 signaling in cancer therapy. Curr. Pharm. Des. 2014; 20(42): 6555-64.
  28. Lancellotti M., Pereira R.F.C., Cury G.G., Hollanda L.M. Pathogenic and opportunistic respiratory bacteria-induced apoptosis. Braz. J. Infect. Dis. 2009; 13(3): 226-31.
  29. Abrahams V.M., Aldo P.B., Murphy S.P., Visintin I., Koga K., Wilson G. et al. TLR6 modulates first trimester trophoblast responses to peptidoglycan. J. Immunol. 2008; 180(9): 6035-43.

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