Expression of the mRNA of the inflammatory component of the immune response in the period of the expected window of implantation in women with recurrent pregnancy loss in the programs of assisted reproductive technologies

К. П. Головатюк, В. Г. Дубініна, О. М. Носенко, Е. Т. Макшаєва, І. Л. Головатюк-Юзефпольська

Abstract


The aim of study. To reveal the peculiarities of mRNA expression of the inflammatory component genes of the immune response in the expected window of the implantation in women with RPL in ART programs.

Material and methods. 240 patients with RPL in ART programs and 100 conditionally healthy fertile women in the control group with the presence in history of at least one childbirth in time and the absence of episodes of miscarriage were examined. The average age of the examined women of the main group was 29.80 ± 0.30 years, the control group – 30.09 ± 0.32 (p >0.05). The average number of cases of involuntary termination of pregnancy after conduction of ART in main group was 3.24 ± 0.11, the average term of termination of pregnancy was 8.15 ± 0.65 weeks.

All women had a paipel-biopsy of the endometrium during the expected implantation window. Samples were frozen at t = -70 °C. until the study. Reverse transcription -polymerase chain reaction was used to study mRNA expression of IL-1β, IL-2, IL-10, Foxp3, TLR9, IL-2Rα cytokine genes in endometrial biopsy obtained on the day of the implantation window.

Results. It was found that the relative level of mRNA expression of IL-1β, IL-2, Foxp3, TLR9, IL-2Rα genes did not differ significantly in patients with RPL in the cycles of VRT and control group. A statistically significant decrease in mRNA expression of the IL-10 gene was noted.

Conclusion. RPL in the treatment of infertile women in ART programs is associated with changes in the transcription profile of the endometrium during the intended implantation window and with a decrease in the expression level of the IL-10 gene mRNA.


Keywords


infertility; recurrent pregnancy loss; assisted reproductive technologies; inflammation; immune response; mRNA; endometrium; implantation window; IL-1β; IL-2; IL-10; Foxp3; TLR9; IL-2Rα

References


Burmenskaya, O.V. Molecular-genetic markers of the immune response in inflammatory diseases of the female reproductive system. Thesis abstract for MD degree; specialty 03.03.03. Moscow (2014): 48 p.

Babbage, S.J., Arkwright, P.D., Vince, G.S., et al. “Cytokine promoter gene polymorphisms and idiopathic recurrent pregnancy loss.” J Reprod Immunol 1 (2001): 21–7.

Bao, S.H., Shuai, W., Tong, J., et al. “Increased Dickkopf-1 expression in patients with unexplained recurrent spontaneous miscarriage.” Clin Exp Immunol 172 (2013): 437–43.

Choi, Y.K., Kwak-Kim, J. “Cytokine gene polymorphisms in recurrent spontaneous abortions: a comprehensive review.” Am J Reprod Immunol 60 (2008): 91–110. DOI: 10.1111/j.1600-0897.2008.00602.x

Ghazaey, S., Keify, F., Mirzaei, F., et al. “Chromosomal analysis of couples with repeated spontaneous abortions in northeastern Іran.” Int J Fertil Steril 9.1 (2015): 47–54.

Gu, Y., Yang, J., Ouyang, X., et al. “Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells.” European journal of immunology 38 (2008): 1807–13. DOI: 10.1002/eji.200838331

Heo, Y.J., Joo, Y.B., Oh, H.J., et al. “IL-10 suppresses Th17 cells and promotes regulatory T cells in the CD4+ T cell population of rheumatoid arthritis patients.” Immunol Lett 127.2 (2010): 150–6. DOI: 10.1016/j.imlet.2009.10.006

Hu, W.T., Huang, L.L., Li, M.Q., et al. “Decidual stromal cell-derived IL-33 contributes to Th2 bias and inhibits decidual NK cell cytotoxicity through NF-κB signaling in human early pregnancy.” J Reprod Immunol 109 (2015): 52–65. DOI: 10.1016/j.jri.2015.01.004

Qaddourah, R.H., Magdoud, K., Saldanha, F.L., et al. “IL-10 gene promoter and intron polymorphisms and changes in IL-10 secretion in women with idiopathic recurrent miscarriage.” Hum Reprod 29 (2014): 1025–34. DOI: 10.1093/humrep/deu043

Saifi, B., Rezaee, S.A., Tajik, N., et al. “Th17 cells and related cytokines in unexplained recurrent spontaneous miscarriage at the implantation window.” Reprod Biomed Online 29 (2014): 481–9. DOI: 10.1016/j.rbmo.2014.06.008

Sakaguchi, S. “Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses.” Annu Rev Immunol 22 (2004): 531–62.

Wang, W.J., Liu, F.J., Qu, H.M., et al. “Regulation of the expression of Th17 cells and regulatory T cells by IL-27 in patients with unexplained early recurrent miscarriage.” J Reprod Immunol 99 (2013): 39–45.

Wang, W.J., Hao, C.F., Yi, L., et al. “Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients.” J Reprod Immnol 84 (2010): 164–70.

Wu, Z., You, Z., Zhang, C., et al. “Association between functional polymorphisms of Foxp3 gene and the occurrence of unexplained recurrent spontaneous abortion in a Chinese Han population.” Clin Dev Immunol (2012): 896458. DOI: 10.1155/2012/896458

Yue, C.Y., Zhang, B., Ying, C.M. “Elevated Serum Level of IL-35 Associated with the Maintenance of Maternal-Fetal Immune Tolerance in Normal Pregnancy.” PloS One 10 (2015): e0128219. DOI: 10.1371/journal.pone.0128219

Zenclussen, A.C., Gerlof, K., Zenclussen, M.L., et al. “Abnormal T-cell reactivity against paternal antigens in spontaneous abortion: adoptive transfer of pregnancy-induced CD4+ CD25+ T regulatory cells prevents fetal rejection in a murine abortion model.” Am J Pathol 166 (2005): 811–22.


GOST Style Citations


1. Бурменская, О.В. Молекулярно-генетические маркеры иммунного ответа при воспалительных заболеваниях органов женской репродуктивной системы: автореф. дисс. … д. биол. н.: 03.03.03 / О.В. Бурменская. – Москва, 2014. – 48 с.

2. Babbage, S.J., Arkwright, P.D., Vince, G.S., et al. “Cytokine promoter gene polymorphisms and idiopathic recurrent pregnancy loss.” J Reprod Immunol 1 (2001): 21–7.

3. Bao, S.H., Shuai, W., Tong, J., et al. “Increased Dickkopf-1 expression in patients with unexplained recurrent spontaneous miscarriage.” Clin Exp Immunol 172 (2013): 437–43.

4. Choi, Y.K., Kwak-Kim, J. “Cytokine gene polymorphisms in recurrent spontaneous abortions: a comprehensive review.” Am J Reprod Immunol 60 (2008): 91–110. DOI: 10.1111/j.1600-0897.2008.00602.x

5. Ghazaey, S., Keify, F., Mirzaei, F., et al. “Chromosomal analysis of couples with repeated spontaneous abortions in northeastern Іran.” Int J Fertil Steril 9.1 (2015): 47–54.

6. Gu, Y., Yang, J., Ouyang, X., et al. “Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells.” European journal of immunology 38 (2008): 1807–13. DOI: 10.1002/eji.200838331

7. Heo, Y.J., Joo, Y.B., Oh, H.J., et al. “IL-10 suppresses Th17 cells and promotes regulatory T cells in the CD4+ T cell population of rheumatoid arthritis patients.” Immunol Lett 127.2 (2010): 150–6. DOI: 10.1016/j.imlet.2009.10.006

8. Hu, W.T., Huang, L.L., Li, M.Q., et al. “Decidual stromal cell-derived IL-33 contributes to Th2 bias and inhibits decidual NK cell cytotoxicity through NF-κB signaling in human early pregnancy.” J Reprod Immunol 109 (2015): 52–65. DOI: 10.1016/j.jri.2015.01.004

9. Qaddourah, R.H., Magdoud, K., Saldanha, F.L., et al. “IL-10 gene promoter and intron polymorphisms and changes in IL-10 secretion in women with idiopathic recurrent miscarriage.” Hum Reprod 29 (2014): 1025–34. DOI: 10.1093/humrep/deu043

10. Saifi, B., Rezaee, S.A., Tajik, N., et al. “Th17 cells and related cytokines in unexplained recurrent spontaneous miscarriage at the implantation window.” Reprod Biomed Online 29 (2014): 481–9. DOI: 10.1016/j.rbmo.2014.06.008

11. Sakaguchi, S. “Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses.” Annu Rev Immunol 22 (2004): 531–62.

12. Wang, W.J., Liu, F.J., Qu, H.M., et al. “Regulation of the expression of Th17 cells and regulatory T cells by IL-27 in patients with unexplained early recurrent miscarriage.” J Reprod Immunol 99 (2013): 39–45.

13. Wang, W.J., Hao, C.F., Yi, L., et al. “Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients.” J Reprod Immnol 84 (2010): 164–70.

14. Wu, Z., You, Z., Zhang, C., et al. “Association between functional polymorphisms of Foxp3 gene and the occurrence of unexplained recurrent spontaneous abortion in a Chinese Han population.” Clin Dev Immunol (2012): 896458. DOI: 10.1155/2012/896458

15. Yue, C.Y., Zhang, B., Ying, C.M. “Elevated Serum Level of IL-35 Associated with the Maintenance of Maternal-Fetal Immune Tolerance in Normal Pregnancy.” PloS One 10 (2015): e0128219. DOI: 10.1371/journal.pone.0128219

16. Zenclussen, A.C., Gerlof, K., Zenclussen, M.L., et al. “Abnormal T-cell reactivity against paternal antigens in spontaneous abortion: adoptive transfer of pregnancy-induced CD4+ CD25+ T regulatory cells prevents fetal rejection in a murine abortion model.” Am J Pathol 166 (2005): 811–22.





DOI: https://doi.org/10.18370/2309-4117.2017.37.26-30

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