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Immunoendocrine Markers of Stress in Seminal Plasma at IVF/ICSI Failure: a Preliminary Study

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Abstract

We have previously shown that high level of seminal interleukin (IL)-18 is positively associated with a greater risk of pregnancy failure in women exposed to their partners’ seminal plasma (SP) during the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle. Since IL-18 and IL-1β considered to be the key immune markers of stress, here we ask whether their increase in SP may be due to the stress experienced by men engaged in the IVF programs. Therefore, we correlated seminal IL-18 with IL-1β and both cytokines with the seminal steroids, whose increase indicates the activation of neuroendocrine stress response systems. Retrospective analysis of stored seminal samples was performed. Based on previously identified cutoff level for content of IL-18 per ejaculate, samples with high IL-18 content from IVF failure group (n = 9), as well as samples with low IL-18 content from IVF success group (n = 7), were included in the study. Seminal cytokines were evaluated using FlowCytomix™ technology. A set of 16 biologically active steroids in SP was quantified by liquid chromatography coupled with mass spectrometry. Concentrations and total amounts per ejaculate of cytokines and steroids were determined. A positive significant correlation was found between the levels of IL-18 and IL-1β. There was also a positive correlation between IL-18 or IL-1β and 17-α-hydroxypregnenolone, 17-α-hydroxyprogesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione, testosterone, dihydrotestosterone, progesterone, corticosterone, 11-deoxycorticosterone, and the ratio of DHEAS/cortisol. We suggested that stress-related overexpression of immune and hormonal factors in SP may be the key link between male stress and embryo implantation failure.

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References

  1. De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T, et al. ART in Europe, 2014: results generated from European registries by ESHRE: the European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). Hum Reprod. 2018;33(9):1586–601.

    PubMed  Google Scholar 

  2. Sengupta J, Ghosh D. Multi-level and multi-scale integrative approach to the understanding of human blastocyst implantation. Prog Biophys Mol Biol. 2014;114(1):49–60.

    CAS  PubMed  Google Scholar 

  3. Edwards RG. Human implantation: the last barrier in assisted reproduction technologies? Reprod BioMed Online. 2006;13(6):887–904.

    PubMed  Google Scholar 

  4. Schjenken JE, Robertson SA. Seminal fluid signalling in the female reproductive tract: implications for reproductive success and offspring health. Adv Exp Med Biol. 2015;868:127–58.

    PubMed  Google Scholar 

  5. Adefuye AO, Adeola HA, Sales KJ, Katz AA. Seminal fluid-mediated inflammation in physiology and pathology of the female reproductive tract. J Immunol Res. 2016;2016:9707252.

    PubMed  PubMed Central  Google Scholar 

  6. Tremellen KP, Seamark RF, Robertson SA. Seminal transforming growth factor beta1 stimulates granulocyte-macrophage colony-stimulating factor production and inflammatory cell recruitment in the murine uterus. Biol Reprod. 1998;58(5):1217–25.

  7. Robertson SA, Ingman WV, O'Leary S, Sharkey DJ, Tremellen KP. Transforming growth factor beta-a mediator of immune deviation in seminal plasma. J Reprod Immunol. 2002;57:109–28.

    CAS  PubMed  Google Scholar 

  8. Robertson SA, Guerin LR, Moldenhauer LM, Hayball JD. Activating T regulatory cells for tolerance in early pregnancy - the contribution of seminal fluid. J Reprod Immunol. 2009;83(1–2):109–16.

    CAS  PubMed  Google Scholar 

  9. Sharkey DJ, Macpherson AM, Tremellen KP, Mottershead DG, Gilchrist RB, Robertson SA. TGF-β mediates proinflammatory seminal fluid signaling in human cervical epithelial cells. J Immunol. 2012;189(2):1024–35.

    CAS  PubMed  Google Scholar 

  10. Clark DA, Rahmati M, Gohner C, Bensussan A, Markert UR, Chaouat G. Seminal plasma peptides may determine maternal immune response that alters success or failure of pregnancy in the abortion-prone CBAxDBA/2 model. J Reprod Immunol. 2013;99(1–2):46–53.

    CAS  PubMed  Google Scholar 

  11. Chen JC, Johnson BA, Erikson DW, Piltonen TT, Barragan F, Chu S, et al. Seminal plasma induces global transcriptomic changes associated with cell migration, proliferation and viability in endometrial epithelial cells and stromal fibroblasts. Hum Reprod. 2014;29(6):1255–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Kim BJ, Choi YM, Rah SY, Park DR, Park SA, Chung YJ, et al. Seminal CD38 is a pivotal regulator for fetomaternal tolerance. Proc Natl Acad Sci U S A. 2015;112(5):1559–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Song ZH, Li ZY, Li DD, Fang WN, Liu HY, Yang DD, et al. Seminal plasma induces inflammation in the uterus through the γδ T/IL-17 pathway. Sci Rep. 2016;6:25118.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Glynn DJ, Heng K, Russell DL, Sharkey DJ, Robertson SA, Anand-Ivell R, et al. Male seminal relaxin contributes to induction of the post-mating cytokine response in the female mouse uterus. Front Physiol. 2017;8:422.

    PubMed  PubMed Central  Google Scholar 

  15. Paktinat S, Hashemi SM, Ghaffari Novin M, Mohammadi-Yeganeh S, Salehpour S, Karamian A, et al. Seminal exosomes induce interleukin-6 and interleukin-8 secretion by human endometrial stromal cells. Eur J Obstet Gynecol Reprod Biol. 2019;235:71–6.

    CAS  PubMed  Google Scholar 

  16. Bromfield JJ, Schjenken JE, Chin PY, Care AS, Jasper MJ, Robertson SA. Maternal tract factors contribute to paternal seminal fluid impact on metabolic phenotype in offspring. Proc Natl Acad Sci U S A. 2014;111(6):2200–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Ata B, Abou-Setta AM, Seyhan A, Buckett W. Application of seminal plasma to female genital tract prior to embryo transfer in assisted reproductive technology cycles (IVF, ICSI and frozen embryo transfer). Cochrane Database Syst Rev. 2018;2:CD011809.

    PubMed  Google Scholar 

  18. Anderson K, Nisenblat V, Norman R. Lifestyle factors in people seeking infertility treatment - a review. Aust N Z J Obstet Gynaecol. 2010;50(1):8–20.

    PubMed  Google Scholar 

  19. Ilacqua A, Izzo G, Emerenziani GP, Baldari C, Aversa A. Lifestyle and fertility: the influence of stress and quality of life on male fertility. Reprod Biol Endocrinol. 2018;16(1):115.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Bhongade MB, Prasad S, Jiloha RC, Ray PC, Mohapatra S, Koner BC. Effect of psychological stress on fertility hormones and seminal quality in male partners of infertile couples. Andrologia. 2015;47(3):336–42.

    CAS  PubMed  Google Scholar 

  21. Nargund VH. Effects of psychological stress on male fertility. Nat Rev Urol. 2015;12(7):373–82.

    CAS  PubMed  Google Scholar 

  22. De Berardis D, Mazza M, Marini S, Del Nibletto L, Serroni N, Pino MC, et al. Psychopathology, emotional aspects and psychological counselling in infertility: a review. Clin Ter. 2014;165(3):163–9.

    PubMed  Google Scholar 

  23. Ying L, Wu LH, Loke AY. Gender differences in emotional reactions to in vitro fertilization treatment: a systematic review. J Assist Reprod Genet. 2016;33(2):167–79.

    PubMed  Google Scholar 

  24. Lakatos E, Szigeti JF, Ujma PP, Sexty R, Balog P. Anxiety and depression among infertile women: a cross-sectional survey from Hungary. BMC Womens Health. 2017;17(1):48.

    PubMed  PubMed Central  Google Scholar 

  25. Clarke RN, Klock SC, Geoghegan A, Travassos DE. Relationship between psychological stress and semen quality among in-vitro fertilization patients. Hum Reprod. 1999;14(3):753–8.

    CAS  PubMed  Google Scholar 

  26. Holley SR, Pasch LA, Bleil ME, Gregorich S, Katz PK, Adler NE. Prevalence and predictors of major depressive disorder for fertility treatment patients and their partners. Fertil Steril. 2015;103(5):1332–9.

    PubMed  PubMed Central  Google Scholar 

  27. Pook M, Tuschen-Caffier B, Krause W. Is infertility a risk factor for impaired male fertility? Hum Reprod. 2004;19(4):954–9.

    CAS  PubMed  Google Scholar 

  28. Vellani E, Colasante A, Mamazza L, Minasi MG, Greco E, Bevilacqua A. Association of state and trait anxiety to semen quality of in vitro fertilization patients: a controlled study. Fertil Steril. 2013;99(6):1565–72.

    PubMed  Google Scholar 

  29. Zhou FJ, Cai YN, Dong YZ. Stress increases the risk of pregnancy failure in couples undergoing IVF. Stress. 2019;22(4):414–20.

    CAS  PubMed  Google Scholar 

  30. Nikolaeva MA, Babayan AA, Stepanova EO, Smolnikova VY, Kalinina EA, Fernández N, et al. The relationship of seminal transforming growth factor-β1 and interleukin-18 with reproductive success in women exposed to seminal plasma during IVF/ICSI treatment. J Reprod Immunol. 2016;117:45–51.

    CAS  PubMed  Google Scholar 

  31. Sugama S, Conti B. Interleukin-18 and stress. Brain Res Rev. 2008;58(1):85–95.

    CAS  PubMed  Google Scholar 

  32. Conti B, Jahng JW, Tinti C, Son JH, Joh TH. Induction of interferon-gamma inducing factor in the adrenal cortex. J Biol Chem. 1997;272(4):2035–7.

    CAS  PubMed  Google Scholar 

  33. Conti B, Sugama S, Kim Y, Tinti C, Kim H, Baker H, et al. Modulation of IL-18 production in the adrenal cortex following acute ACTH or chronic corticosterone treatment. Neuroimmunomodulation. 2000;8(1):1–7.

    CAS  PubMed  Google Scholar 

  34. Sekiyama A, Ueda H, Kashiwamura S, Nishida K, Kawai K, Teshima-kondo S, et al. IL-18; a cytokine translates a stress into medical science. J Med Investig. 2005;52(Suppl):236–9.

    Google Scholar 

  35. Sekiyama A, Ueda H, Kashiwamura S, Nishida K, Yamaguchi S, Sasaki H, et al. A role of the adrenal gland in stress-induced up-regulation of cytokines in plasma. J Neuroimmunol. 2006;171(1–2):38–44.

    CAS  PubMed  Google Scholar 

  36. Sugama S, Wang N, Shimokawa N, Koibuchi N, Fujita M, Hashimoto M, et al. The adrenal gland is a source of stress-induced circulating IL-18. J Neuroimmunol. 2006;172(1–2):59–65.

    CAS  PubMed  Google Scholar 

  37. Johnson JD, Campisi J, Sharkey CM, Kennedy SL, Nickerson M, Greenwood BN, et al. Catecholamines mediate stress-induced increases in peripheral and central inflammatory cytokines. Neuroscience. 2005;135(4):1295–307.

    CAS  PubMed  Google Scholar 

  38. Cox SS, Speaker KJ, Beninson LA, Craig WC, Paton MM, Fleshner M. Adrenergic and glucocorticoid modulation of the sterile inflammatory response. Brain Behav Immun. 2014;36:183–92.

    CAS  PubMed  Google Scholar 

  39. Fleshner M, Crane CR. Exosomes, DAMPs and miRNA: features of stress physiology and immune homeostasis. Trends Immunol. 2017;38(10):768–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Maslanik T, Mahaffey L, Tannura K, Beninson L, Greenwood BN, Fleshner M. The inflammasome and danger associated molecular patterns (DAMPs) are implicated in cytokine and chemokine responses following stressor exposure. Brain Behav Immun. 2013;28:54–62.

    CAS  PubMed  Google Scholar 

  41. White CW, Xie JH, Ventura S. Age-related changes in the innervation of the prostate gland: implications for prostate cancer initiation and progression. Organogenesis. 2013;9(3):206–15.

    PubMed  PubMed Central  Google Scholar 

  42. Sastry BV, Janson VE, Owens LK. Significance of substance P- and enkephalin-peptide systems in the male genital tract. Ann N Y Acad Sci. 1991;632:339–53.

    CAS  PubMed  Google Scholar 

  43. Fait G, Vered Y, Yogev L, Gamzu R, Lessing JB, Paz G, et al. High levels of catecholamines in human semen: a preliminary study. Andrologia. 2001;33(6):347–50.

    CAS  PubMed  Google Scholar 

  44. Sternberg EM. Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens. Nat Rev Immunol. 2006;6(4):318–28.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Nguyen AD, Conley AJ. Adrenal androgens in humans and nonhuman primates: production, zonation and regulation. Endocr Dev. 2008;13:33–54.

    CAS  PubMed  Google Scholar 

  46. Kamin HS, Kertes DA. Cortisol and DHEA in development and psychopathology. Horm Behav. 2017;89:69–85.

  47. Lennartsson AK, Kushnir MM, Bergquist J, Billig H, Jonsdottir IH. Sex steroid levels temporarily increase in response to acute psychosocial stress in healthy men and women. Int J Psychophysiol. 2012;84(3):246–53.

    PubMed  Google Scholar 

  48. Bae YJ, Kratzsch J, Zeidler R, Fikenzer S, Werner C, Herm J, et al. Unraveling the steroid hormone response in male marathon runners: correlation of running time with aldosterone and progesterone. J Steroid Biochem Mol Biol. 2019;195:105473.

    CAS  PubMed  Google Scholar 

  49. Bae YJ, Reinelt J, Netto J, Uhlig M, Willenberg A, Ceglarek U, et al. Salivary cortisone, as a biomarker for psychosocial stress, is associated with state anxiety and heart rate. Psychoneuroendocrinology. 2019;101:35–41.

    CAS  PubMed  Google Scholar 

  50. Elman I, Breier A. Effects of acute metabolic stress on plasma progesterone and testosterone in male subjects: relationship to pituitary-adrenocortical axis activation. Life Sci. 1997;61(17):1705–12.

    CAS  PubMed  Google Scholar 

  51. Schumacher M, Mattern C, Ghoumari A, Oudinet JP, Liere P, Labombarda F, et al. Revisiting the roles of progesterone and allopregnanolone in the nervous system: resurgence of the progesterone receptors. Prog Neurobiol. 2014;113:6–39.

    CAS  PubMed  Google Scholar 

  52. Chichinadze K, Chichinadze N. Stress-induced increase of testosterone: contributions of social status and sympathetic reactivity. Physiol Behav. 2008;94:595–603.

    CAS  PubMed  Google Scholar 

  53. World Health Organization (2010) WHO laboratory manual for the examination and processing of human semen. 5th ed. World Health Organization, Geneva

  54. Hacker-Klom UB, Göhde W, Nieschlag E, Behre HM. DNA flow cytometry of human semen. Hum Reprod. 1999;14(10):2506–12.

    CAS  PubMed  Google Scholar 

  55. Steptoe A, Hamer M, Chida Y. The effects of acute psychological stress on circulating inflammatory factors in humans: a review and meta-analysis. Brain Behav Immun. 2007;21:901–12.

    CAS  PubMed  Google Scholar 

  56. Goshen I, Yirmiya R. Interleukin-1 (IL-1): a central regulator of stress responses. Front Neuroendocrinol. 2009;30(1):30–45.

    CAS  PubMed  Google Scholar 

  57. Marsland AL, Walsh C, Lockwood K, John-Henderson NA. The effects of acute psychological stress on circulating and stimulated inflammatory markers: a systematic review and meta-analysis. Brain Behav Immun. 2017;64:208–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Fleshner M, Frank M, Maier SF. Danger signals and inflammasomes: stress-evoked sterile inflammation in mood disorders. Neuropsychopharmacology. 2017;42(1):36–45.

    CAS  PubMed  Google Scholar 

  59. La Fratta I, Tatangelo R, Campagna G, Rizzuto A, Franceschelli S, Ferrone A, et al. The plasmatic and salivary levels of IL-1β, IL-18 and IL-6 are associated to emotional difference during stress in young male. Sci Rep. 2018;8(1):3031.

    PubMed  PubMed Central  Google Scholar 

  60. Matalliotakis IM, Cakmak H, Fragouli Y, Kourtis A, Arici A, Huszar G. Increased IL-18 levels in seminal plasma of infertile men with genital tract infections. Am J Reprod Immunol. 2006;55:428–33.

    CAS  PubMed  Google Scholar 

  61. Qian L, Zhou Y, Du C, Wen J, Teng S, Teng Z. IL-18 levels in the semen of male infertility: semen analysis. Int J Biol Macromol. 2014;64:190–2.

    CAS  PubMed  Google Scholar 

  62. Dhabhar FS. Effects of stress on immune function: the good, the bad, and the beautiful. Immunol Res. 2014;58(2–3):193–210.

    CAS  PubMed  Google Scholar 

  63. Breen MS, Beliakova-Bethell N, Mujica-Parodi LR, Carlson JM, Ensign WY, Woelk CH, et al. Acute psychological stress induces short-term variable immune response. Brain Behav Immun. 2016;53:172–82.

    CAS  PubMed  Google Scholar 

  64. Rohleder N. Stress and inflammation - the need to address the gap in the transition between acute and chronic stress effects. Psychoneuroendocrinology. 2019;105:164–71.

    PubMed  Google Scholar 

  65. Lennartsson AK, Kushnir MM, Bergquist J, Jonsdottir IH. DHEA and DHEA-S response to acute psychosocial stress in healthy men and women. Biol Psychol. 2012;90(2):143–9.

    PubMed  Google Scholar 

  66. Kalimi M, Shafagoj Y, Loria RM, Padgett D, Regelson W. Anti-glucocorticoid effects of dehydroepiandrosterone (DHEA). Mol Cell Biochem. 1994;131:99–104.

    CAS  PubMed  Google Scholar 

  67. Theorell T. Anabolism and catabolism - antagonistic partners in stress and strain. SJWEH Supplement. 2008:136–43.

  68. Maninger N, Wolkowitz OM, Reus VI, Epel ES, Mellon SH. Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). Front Neuroendocrinol. 2009;30:65–91.

    CAS  PubMed  Google Scholar 

  69. Hechter O, Grossman A, Chatterton RT Jr. Relationship of dehydroepiandrosterone and cortisol in disease. Med Hypotheses. 1997;49:85–91.

    CAS  PubMed  Google Scholar 

  70. Morgan CA 3rd, Southwick S, Hazlett G, Rasmusson A, Hoyt G, Zimolo Z, et al. Relationships among plasma dehydroepiandrosterone sulfate and cortisol levels, symptoms of dissociation, and objective performance in humans exposed to acute stress. Arch Gen Psychiatry. 2004;61:819–25.

    CAS  PubMed  Google Scholar 

  71. Izawa S, Sugaya N, Shirotsuki K, Yamada KC, Ogawa N, Ouchi Y, et al. Salivary dehydroepiandrosterone secretion in response to acute psychosocial stress and its correlations with biological and psychological changes. Biol Psychol. 2008;79:294–8.

    PubMed  Google Scholar 

  72. Oberbeck R, Benschop RJ, Jacobs R, Hosch W, Jetschmann JU, Schürmeyer TH, et al. Endocrine mechanisms of stress-induced DHEA-secretion. J Endocrinol Investig. 1998;21(3):148–53.

    CAS  Google Scholar 

  73. Jeckel CM, Lopes RP, Berleze MC, Luz C, Feix L, Argimon II, et al. Neuroendocrine and immunological correlates of chronic stress in ‘strictly healthy’ populations. Neuroimmunomodulation. 2010;17:9–18.

    PubMed  Google Scholar 

  74. Russell G, Lightman S. The human stress response. Nat Rev Endocrinol. 2019;15(9):525–34.

    PubMed  Google Scholar 

  75. Lam JCW, Shields GS, Trainor BC, Slavich GM, Yonelinas AP. Greater lifetime stress exposure predicts blunted cortisol but heightened DHEA responses to acute stress. Stress Health. 2019;35(1):15–26.

    PubMed  Google Scholar 

  76. McCarty R, Horwatt K, Konarska M. Chronic stress and sympathetic-adrenal medullary responsiveness. Soc Sci Med. 1988;26(3):333–41.

    CAS  PubMed  Google Scholar 

  77. Schreier HM, Chen E. Low-grade inflammation and ambulatory cortisol in adolescents: interaction between interviewer-rated versus self-rated acute stress and chronic stress. Psychosom Med. 2017;79(2):133–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Kreuz LE, Rose RM, Jennings JR. Suppression of plasma testosterone levels and psychological stress. A longitudinal study of young men in officer candidate school. Arch Gen Psychiatry. 1972;26:479–82.

    CAS  PubMed  Google Scholar 

  79. Theorell T, Karasek RA, Eneroth P. Job strain variations in relation to plasma testosterone fluctuations in working men—a longitudinal study. J Intern Med. 1990;227:31–6.

    CAS  PubMed  Google Scholar 

  80. Damián JP, Bausero M, Bielli A. Acute stress, hypothalamic-hypophyseal-gonadal axis and testicular function – a review. Ann Anim Sci. 2015;15(1):31–50.

    Google Scholar 

  81. Mora F, Segovia G, Del Arco A, de Blas M, Garrido P. Stress, neurotransmitters, corticosterone and body-brain integration. Brain Res. 2012;1476:71–85.

    CAS  PubMed  Google Scholar 

  82. Elzanaty S, Malm J. Comparison of semen parameters in samples collected by masturbation at a clinic and at home. Fertil Steril. 2008;89(6):1718–22.

    PubMed  Google Scholar 

  83. Fishel S, Webster J, Jackson P, Faratian B. Evaluation of high vaginal insemination at oocyte recovery in patients undergoing in vitro fertilization. Fertil Steril. 1989;51:135–8.

    CAS  PubMed  Google Scholar 

  84. 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;30:569–74.

    PubMed  PubMed Central  Google Scholar 

  85. 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;30:907–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Mayer RB, Ebner T, Yaman C, Hartl J, Sir A, Krain V, et al. Influence of intracervical and intravaginal seminal plasma on the endometrium in assisted reproduction: a double-blind, placebo-controlled, randomized study. Ultrasound Obstet Gynecol. 2015;45(2):132–8.

    CAS  PubMed  Google Scholar 

  87. Jafarabadi M, Sasani A, Ramezanzadeh F, Zandieh Z, Shariat M, Haghollahi F. Intracervical application of seminal plasma at the time of oocyte pickup during in vitro fertilization. Acta Medica Mediterranea. 2016;32:2085–90.

    Google Scholar 

  88. Niitsu K, Rice MJ, Houfek JF, Stoltenberg SF, Kupzyk KA, Barron CR. A systematic review of genetic influence on psychological resilience. Biol Res Nurs. 2019;21(1):61–71.

    CAS  PubMed  Google Scholar 

  89. George AF, Jang KS, Nyegaard M, Neidleman J, Spitzer TL, Xie G, et al. Seminal plasma promotes decidualization of endometrial stromal fibroblasts in vitro from women with and without inflammatory disorders in a manner dependent on interleukin-11 signaling. Hum Reprod. 2020;35(3):617–40.

    CAS  PubMed  Google Scholar 

  90. Lédée-Bataille N, Bonnet-Chea K, Hosny G, Dubanchet S, Frydman R, Chaouat G. Role of the endometrial tripod interleukin-18, -15, and -12 in inadequate uterine receptivity in patients with a history of repeated in vitro fertilization-embryo transfer failure. Fertil Steril. 2005;83:598–605.

    PubMed  Google Scholar 

  91. Liu HY, Liu ZK, Chao H, Li Z, Song Z, Yang Y, et al. High-dose interferon-γ promotes abortion in mice by suppressing Treg and Th17 polarization. J Interf Cytokine Res. 2014;34(5):394–403.

    CAS  Google Scholar 

  92. Inagaki N, Stern C, McBain J, Lopata A, Kornman L, Wilkinson D. Analysis of intra-uterine cytokine concentration and matrix-metalloproteinase activity in women with recurrent failed embryo transfer. Hum Reprod. 2003;18(3):608–15.

    CAS  PubMed  Google Scholar 

  93. Boomsma CM, Kavelaars A, Eijkemans MJ, Lentjes EG, Fauser BC, Heijnen CJ, et al. Endometrial secretion analysis identifies a cytokine profile predictive of pregnancy in IVF. Hum Reprod. 2009;24(6):1427–35.

    CAS  PubMed  Google Scholar 

  94. Wang H, Shi G, Li M, Fan H, Ma H, Sheng L. Correlation of IL-1 and HB-EGF with endometrial receptivity. Exp Ther Med. 2018;16(6):5130–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Frank GR, Brar AK, Jikihara H, Cedars MI, Handwerger S. Interleukin-1 beta and the endometrium: an inhibitor of stromal cell differentiation and possible autoregulator of decidualization in humans. Biol Reprod. 1995;52(1):184–91.

    CAS  PubMed  Google Scholar 

  96. Taylor HS. The role of HOX genes in human implantation. Hum Reprod Update. 2000;6(1):75–9.

    CAS  PubMed  Google Scholar 

  97. Sarno JL, Schatz F, Lockwood CJ, Huang ST, Taylor HS. Thrombin and interleukin-1beta regulate HOXA10 expression in human term decidual cells: implications for preterm labor. J Clin Endocrinol Metab. 2006;91(6):2366–72.

    CAS  PubMed  Google Scholar 

  98. Diao HL, Su RW, Tan HN, Li SJ, Lei W, Deng WB, et al. Effects of androgen on embryo implantation in the mouse delayed-implantation model. Fertil Steril. 2008;90(4 Suppl):1376–83.

    CAS  PubMed  Google Scholar 

  99. Robertson SA, Mau VJ, Tremellen KP, Seamark RF. Role of high molecular weight seminal vesicle proteins in eliciting the uterine inflammatory response to semen in mice. J Reprod Fertil. 1996;107(2):265–77.

    CAS  PubMed  Google Scholar 

  100. Cermik D, Selam B, Taylor HS. Regulation of HOXA-10 expression by testosterone in vitro and in the endometrium of patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88(1):238–43.

    CAS  PubMed  Google Scholar 

  101. Frolova AI, O'Neill K, Moley KH. Dehydroepiandrosterone inhibits glucose flux through the pentose phosphate pathway in human and mouse endometrial stromal cells, preventing decidualization and implantation. Mol Endocrinol. 2011;25(8):1444–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Rodriguez-Caro H, Dragovic R, Shen M, Dombi E, Mounce G, Field K, et al. In vitro decidualisation of human endometrial stromal cells is enhanced by seminal fluid extracellular vesicles. J Extracell Vesicles. 2019;8(1):1565262.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Cicinelli E, de Ziegler D. Transvaginal progesterone: evidence for a new functional 'portal system' flowing from the vagina to the uterus. Hum Reprod Update. 1999;5:365–72.

    CAS  PubMed  Google Scholar 

  104. Nikolaeva M, Babayan A, Stepanova E, Arefieva A, Dontsova T, Smolnikova V, et al. The link between seminal cytokine interleukin 18, female circulating regulatory T cells, and IVF/ICSI success. Reprod Sci. 2019;26(8):1034–44.

    CAS  PubMed  Google Scholar 

  105. Haimovici F, Anderson JL, Bates GW, Racowsky C, Ginsburg ES, Simovici D, et al. Stress, anxiety, and depression of both partners in infertile couples are associated with cytokine levels and adverse IVF outcome. Am J Reprod Immunol. 2018;79(4):e12832.

    PubMed  Google Scholar 

  106. Hampl R, Kubátová J, Sobotka V, Herácek J. Steroids in semen, their role in spermatogenesis, and the possible impact of endocrine disruptors. Horm Mol Biol Clin Invest. 2013;13(1):1–5.

    CAS  Google Scholar 

  107. Vitku J, Kolatorova L, Hampl R. Occurrence and reproductive roles of hormones in seminal plasma. Basic Clin Androl. 2017;27:19.

    PubMed  PubMed Central  Google Scholar 

  108. Zufferey F, Rahban R, Garcia A, Gagnebin Y, Boccard J, Tonoli D, et al. Steroid profiles in both blood serum and seminal plasma are not correlated and do not reflect sperm quality: study on the male reproductive health of fifty young Swiss men. Clin Biochem. 2018;62:39–46.

    CAS  PubMed  Google Scholar 

  109. Trussell JC, Coward RM, Santoro N, Stetter C, Kunselman A, Diamond MP, et al. Association between testosterone, semen parameters, and live birth in men with unexplained infertility in an intrauterine insemination population. Fertil Steril. 2019;111(6):1129–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Antoniassi MP, Intasqui P, Camargo M, Zylbersztejn DS, Carvalho VM, Cardozo KH, et al. Analysis of the functional aspects and seminal plasma proteomic profile of sperm from smokers. BJU Int. 2016;118(5):814–22.

    CAS  PubMed  Google Scholar 

  111. Fan W, Xu Y, Liu Y, Zhang Z, Lu L, Ding Z. Obesity or overweight, a chronic inflammatory status in male reproductive system, leads to mice and human subfertility. Front Physiol. 2018;8:1117.

    PubMed  PubMed Central  Google Scholar 

  112. Leisegang K, Henkel R, Agarwal A. Obesity and metabolic syndrome associated with systemic inflammation and the impact on the male reproductive system. Am J Reprod Immunol. 2019;82(5):e13178.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Clinical Immunology, National Medical Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of Russian Federation, Oparina str. 4, Moscow, Russia, 117997

    Marina Nikolaeva, Alla Arefieva, Lubov Krechetova & Gennady Sukhikh

  2. Department of Assisted Technologies in Treatment of Infertility, National Medical Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of Russian Federation, Oparina str. 4, Moscow, Russia, 117997

    Alina Babayan & Elena Kalinina

  3. Department of Systems Biology, National Medical Research Center for Obstetrics, Gynecology and Perinatology of Ministry of Healthcare of Russian Federation, Oparina str. 4, Moscow, Russia, 117997

    Vitaliy Chagovets, Natalia Kitsilovskaya, Natalia Starodubtseva & Vladimir Frankevich

  4. Moscow Institute of Physics and Technology, Institutskiy per. 9, Dolgoprudny, Moscow, Russia, 141701

    Natalia Starodubtseva

  5. First Moscow State Medical University named after I.M. Sechenov, Trubetskaya str. 8-2, Moscow, Russia, 119991

    Gennady Sukhikh

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  1. Marina Nikolaeva
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  2. Alla Arefieva
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  3. Alina Babayan
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  4. Vitaliy Chagovets
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  6. Natalia Starodubtseva
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  7. Vladimir Frankevich
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  8. Elena Kalinina
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  9. Lubov Krechetova
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  10. Gennady Sukhikh
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Correspondence to Marina Nikolaeva.

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Nikolaeva, M., Arefieva, A., Babayan, A. et al. Immunoendocrine Markers of Stress in Seminal Plasma at IVF/ICSI Failure: a Preliminary Study. Reprod. Sci. 28, 144–158 (2021). https://doi.org/10.1007/s43032-020-00253-z

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  • DOI: https://doi.org/10.1007/s43032-020-00253-z

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