T Cell Subsets Profiling in Unexplained Infertile Women with Successful and Unsuccessful in Vitro Fertilization Outcome: Focus on the Effect of Seminal Plasma
Abstract
Unexplained infertility (UI) is one of the most common diagnoses in the fertility care. Seminal plasma (SP) plays a crucial role in the regulation of female immune responses and the success of a pregnancy. In vitro fertilization (IVF) is a well-known method for the treatment of UI. In this study, we aimed to investigate the effect of SP on the differentiation of T helper (Th) cell subsets and the relationship between these subsets with the rate of IVF success in a group of women complicated with UI compared to those with normal pregnancy. This study was conducted on 20 UI couples (ten with successful and ten with unsuccessful IVF outcome) and 10 fertile couples as the control group. Four color flow cytometry technique was used to detect Th cell subsets in the peripheral blood mononuclear cells (PBMC) with or without stimulation by SP. Results indicated that the frequencies of IL-17+ and Foxp3+ T cells after incubation with SP was significantly increased in couples with unsuccessful IVF outcome as compared to successful and healthy groups (p<0.05). Additionally, a positive correlation was observed between Th1 and Th2 cells in the unsuccessful IVF group (R=0.6, p=0.03). In summary, the results of the present study demonstrated that exposure to SP might increase Th17 and Treg cell frequencies in infertile women with unsuccessful IVF, and might also balance inflammatory to regulatory responses to finally tune-up the Th1/Th2/Th17/Treg balance and support the success of IVF.
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2. Quaas A, Dokras A. Diagnosis and treatment of unexplained infertility. Reviews in obstetrics and gynecology 2008;1(2):69.
3. Graham R, Seif M, Aplin J, Li T, Cooke I, Rogers A, et al. An endometrial factor in unexplained infertility. Bmj 1990;300(6737):1428-31.
4. Lessey BA, Castelbaum AJ, Sawin SW, Sun J. Integrins as markers of uterine receptivity in women with primary unexplained infertility. Fertil Steril1995;63(3):535-42.
5. Edi-Osagie EC, Seif MW, Aplin JD, Jones CJ, Wilson G, Lieberman BA. Characterizing the endometrium in unexplained and tubal factor infertility: a multiparametric investigation. Fertil Steril 2004;82(5):1379-89.
6. Wegmann TG, Lin H, Guilbert L, Mosmann TR. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol Today 1993;14(7):353-6.
7. Figueiredo AS, Schumacher A. The T helper type 17/regulatory T cell paradigm in pregnancy. Immunology 2016;148(1):13-21.
8. Wang WJ, Hao CF, Yi L, Yin GJ, Bao SH, Qiu LH, et al. Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients. J Reprod Immunol 2010;84(2):164-70.
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11. Zenclussen AC. CD4+ CD25+ T regulatory cells in murine pregnancy. J Reprod Immunol 2005;65(2):101-10.
12. Wang W-J, Hao C-F, Yin G-J, Bao S-H, Qiu L-H, Lin Q-D. Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients. J Reprod Immunol 2010;84(2):164-70.
13. Chicea R, Ispasoiu F, Focsa M. Seminal plasma insemination during ovum-pickup--a method to increase pregnancy rate in IVF/ICSI procedure. A pilot randomized trial. J Assist Reprod Genet 2013;30(4):569-74.
14. Friedler S, Ben-Ami I, Gidoni Y, Strassburger D, Kasterstein E, Maslansky B, et al. Effect of seminal plasma application to the vaginal vault in in vitro fertilization or intracytoplasmic sperm injection treatment cycles-a double-blind, placebo-controlled, randomized study. J Assist Reprod Genet 2013;30(7):907-11.
15. Crawford G, Ray A, Gudi A, Shah A, Homburg R. The role of seminal plasma for improved outcomes during in vitro fertilization treatment: review of the literature and meta-analysis. Hum Reprod Update2015;21(2):275-84.
16. Nawroth F, Von Wolff M. Seminal plasma activity to improve implantation in In vitro Fertilisation–how can it be used in daily practice? Front Endocrinol (Lausanne) 2018;9:208.
17. Kanannejad Z, Gharesi‐Fard BJA. Difference in the seminal plasma protein expression in unexplained infertile men with successful and unsuccessful in vitro fertilisation outcome. Andrologia2019; 5191):e13158.
18. Robertson SA, Sharkey DJ. Seminal fluid and fertility in women. Fertil Steril 2016;106(3):511-9.
19. Robertson SA, Sharkey DJ. Seminal fluid and fertility in women. Fertil Steril 2016;106(3):511-9.
20. Sharkey DJ, Tremellen KP, Jasper MJ, Gemzell-Danielsson K, Robertson SA. Seminal fluid induces leukocyte recruitment and cytokine and chemokine mRNA expression in the human cervix after coitus. J Immunol 2012;188(5):2445-54.
21. Guerin LR, Prins JR, Robertson SA. Regulatory T-cells and immune tolerance in pregnancy: a new target for infertility treatment? Hum Reprod Update 2009;15(5):517-35.
22. Tremellen KP, Valbuena D, Landeras J, Ballesteros A, Martinez J, Mendoza S, et al. The effect of intercourse on pregnancy rates during assisted human reproduction. Hum Reprod 2000;15(12):2653-8.
23. Azad M, Keshtgar S, Jahromi BN, Kanannejad Z, Gharesi-Fard B. T helper cell subsets and related cytokines in infertile women undergoing in vitro fertilization before and after seminal plasma exposure. Clin Exp Reprod Med 2017;44(4):214-23.
24. Templeton AA, Mortimer DJF, sterility. The development of a clinical test of sperm migration to the site of fertilization. Fertil Steril1982;37(3):410-5.
25. Aitken R, Elton RJR. Significance of Poisson distribution theory in analysing the interaction between human spermatozoa and zona-free hamster oocytes. J Reprod Fertil1984;72(2):311-21.
26. Aitken RJ, Best FS, Richardson DW, Djahanbakhch O, Mortimer D, Templeton AA, et al. An analysis of sperm function in cases of unexplained infertility: conventional criteria, movement characteristics, and fertilizing capacity. Fertil Steril1982;38(2):212-21.
27. Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update 2010;16(3):231-45.
28. Nasri F, Doroudchi M, Namavar Jahromi B, Gharesi-Fard B. T Helper Cells Profile and CD4+CD25+Foxp3+Regulatory T Cells in Polycystic Ovary Syndrome. Iran J Immunol 2018;15(3):175-85.
29. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Annu Rev Immunol 2009;27:485-517.
30. Lissauer D, Goodyear O, Khanum R, Moss PA, Kilby MD. Profile of maternal CD4 T-cell effector function during normal pregnancy and in women with a history of recurrent miscarriage. Clin Sci (Lond) 2014;126(5):347-54.
31. Lombardelli L, Logiodice F, Aguerre-Girr M, Kullolli O, Haller H, Casart Y, et al. Interleukin-17-producing decidual CD4+ T cells are not deleterious for human pregnancy when they also produce interleukin-4. Clin Mol Allergy 2016;14:1.
32. Song Z-H, Li Z-Y, Li D-D, Fang W-N, Liu H-Y, Yang D-D, et al. Seminal plasma induces inflammation in the uterus through the γδ T/IL-17 pathway. Sci Rep 2016;6:25118.
33. Yamakawa K, Yoshida K, Nishikawa H, Kato T, Iwamoto T. Comparative analysis of interindividual variations in the seminal plasma proteome of fertile men with identification of potential markers for azoospermia in infertile patients. J Androl 2007;28(6):858-65.
2. Quaas A, Dokras A. Diagnosis and treatment of unexplained infertility. Reviews in obstetrics and gynecology 2008;1(2):69.
3. Graham R, Seif M, Aplin J, Li T, Cooke I, Rogers A, et al. An endometrial factor in unexplained infertility. Bmj 1990;300(6737):1428-31.
4. Lessey BA, Castelbaum AJ, Sawin SW, Sun J. Integrins as markers of uterine receptivity in women with primary unexplained infertility. Fertil Steril1995;63(3):535-42.
5. Edi-Osagie EC, Seif MW, Aplin JD, Jones CJ, Wilson G, Lieberman BA. Characterizing the endometrium in unexplained and tubal factor infertility: a multiparametric investigation. Fertil Steril 2004;82(5):1379-89.
6. Wegmann TG, Lin H, Guilbert L, Mosmann TR. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol Today 1993;14(7):353-6.
7. Figueiredo AS, Schumacher A. The T helper type 17/regulatory T cell paradigm in pregnancy. Immunology 2016;148(1):13-21.
8. Wang WJ, Hao CF, Yi L, Yin GJ, Bao SH, Qiu LH, et al. Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients. J Reprod Immunol 2010;84(2):164-70.
9. Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T‐cell paradigm in pregnancy. Am J Reprod Immunol 2010;63(6):601-10.
10. Sasaki Y, Sakai M, Miyazaki S, Higuma S, Shiozaki A, Saito S. Decidual and peripheral blood CD4+ CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases. Mol Hum Reprod 2004;10(5):347-53.
11. Zenclussen AC. CD4+ CD25+ T regulatory cells in murine pregnancy. J Reprod Immunol 2005;65(2):101-10.
12. Wang W-J, Hao C-F, Yin G-J, Bao S-H, Qiu L-H, Lin Q-D. Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients. J Reprod Immunol 2010;84(2):164-70.
13. Chicea R, Ispasoiu F, Focsa M. Seminal plasma insemination during ovum-pickup--a method to increase pregnancy rate in IVF/ICSI procedure. A pilot randomized trial. J Assist Reprod Genet 2013;30(4):569-74.
14. Friedler S, Ben-Ami I, Gidoni Y, Strassburger D, Kasterstein E, Maslansky B, et al. Effect of seminal plasma application to the vaginal vault in in vitro fertilization or intracytoplasmic sperm injection treatment cycles-a double-blind, placebo-controlled, randomized study. J Assist Reprod Genet 2013;30(7):907-11.
15. Crawford G, Ray A, Gudi A, Shah A, Homburg R. The role of seminal plasma for improved outcomes during in vitro fertilization treatment: review of the literature and meta-analysis. Hum Reprod Update2015;21(2):275-84.
16. Nawroth F, Von Wolff M. Seminal plasma activity to improve implantation in In vitro Fertilisation–how can it be used in daily practice? Front Endocrinol (Lausanne) 2018;9:208.
17. Kanannejad Z, Gharesi‐Fard BJA. Difference in the seminal plasma protein expression in unexplained infertile men with successful and unsuccessful in vitro fertilisation outcome. Andrologia2019; 5191):e13158.
18. Robertson SA, Sharkey DJ. Seminal fluid and fertility in women. Fertil Steril 2016;106(3):511-9.
19. Robertson SA, Sharkey DJ. Seminal fluid and fertility in women. Fertil Steril 2016;106(3):511-9.
20. Sharkey DJ, Tremellen KP, Jasper MJ, Gemzell-Danielsson K, Robertson SA. Seminal fluid induces leukocyte recruitment and cytokine and chemokine mRNA expression in the human cervix after coitus. J Immunol 2012;188(5):2445-54.
21. Guerin LR, Prins JR, Robertson SA. Regulatory T-cells and immune tolerance in pregnancy: a new target for infertility treatment? Hum Reprod Update 2009;15(5):517-35.
22. Tremellen KP, Valbuena D, Landeras J, Ballesteros A, Martinez J, Mendoza S, et al. The effect of intercourse on pregnancy rates during assisted human reproduction. Hum Reprod 2000;15(12):2653-8.
23. Azad M, Keshtgar S, Jahromi BN, Kanannejad Z, Gharesi-Fard B. T helper cell subsets and related cytokines in infertile women undergoing in vitro fertilization before and after seminal plasma exposure. Clin Exp Reprod Med 2017;44(4):214-23.
24. Templeton AA, Mortimer DJF, sterility. The development of a clinical test of sperm migration to the site of fertilization. Fertil Steril1982;37(3):410-5.
25. Aitken R, Elton RJR. Significance of Poisson distribution theory in analysing the interaction between human spermatozoa and zona-free hamster oocytes. J Reprod Fertil1984;72(2):311-21.
26. Aitken RJ, Best FS, Richardson DW, Djahanbakhch O, Mortimer D, Templeton AA, et al. An analysis of sperm function in cases of unexplained infertility: conventional criteria, movement characteristics, and fertilizing capacity. Fertil Steril1982;38(2):212-21.
27. Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update 2010;16(3):231-45.
28. Nasri F, Doroudchi M, Namavar Jahromi B, Gharesi-Fard B. T Helper Cells Profile and CD4+CD25+Foxp3+Regulatory T Cells in Polycystic Ovary Syndrome. Iran J Immunol 2018;15(3):175-85.
29. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Annu Rev Immunol 2009;27:485-517.
30. Lissauer D, Goodyear O, Khanum R, Moss PA, Kilby MD. Profile of maternal CD4 T-cell effector function during normal pregnancy and in women with a history of recurrent miscarriage. Clin Sci (Lond) 2014;126(5):347-54.
31. Lombardelli L, Logiodice F, Aguerre-Girr M, Kullolli O, Haller H, Casart Y, et al. Interleukin-17-producing decidual CD4+ T cells are not deleterious for human pregnancy when they also produce interleukin-4. Clin Mol Allergy 2016;14:1.
32. Song Z-H, Li Z-Y, Li D-D, Fang W-N, Liu H-Y, Yang D-D, et al. Seminal plasma induces inflammation in the uterus through the γδ T/IL-17 pathway. Sci Rep 2016;6:25118.
33. Yamakawa K, Yoshida K, Nishikawa H, Kato T, Iwamoto T. Comparative analysis of interindividual variations in the seminal plasma proteome of fertile men with identification of potential markers for azoospermia in infertile patients. J Androl 2007;28(6):858-65.
| Files | ||
| Issue | Vol 18, No 2 (2019) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v18i2.919 | |
| Keywords | ||
| Flow cytometry In vitro fertilization Seminal plasma T helper subsets Unexplained infertility | ||
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How to Cite
1.
Kanannejad Z, Namavar Jahromi B, Gharesi-Fard B. T Cell Subsets Profiling in Unexplained Infertile Women with Successful and Unsuccessful in Vitro Fertilization Outcome: Focus on the Effect of Seminal Plasma. Iran J Allergy Asthma Immunol. 2019;18(2):163-172.
