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Role of Seminal Plasma in Human Female Reproductive Failure: Immunomodulation, Inflammation, and Infections

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The Male Role in Pregnancy Loss and Embryo Implantation Failure

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 868))

Abstract

Human seminal plasma contains factors that can regulate the female immune system and potentially promote reproductive fitness. Adverse effects on fertility and pregnancy may occur when seminal plasma provides insufficient, excessive, or altered signals or when the female partner is incapable of receiving these signals.

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References

  • Anderson DJ (2007) Genitourinary immune defense. In: Holmes K, Sparling P, Stamm W, Piot P, Wasserheit J, Corey L, Cohen M (eds) Sexually transmitted diseases, 4th edn. McGraw-Hill, New York, NY, pp 271–288

    Google Scholar 

  • Anderson DJ, Pudney J (2005) Mucosal immunology of the human male genital tract and experimental models. In: Mestecky J, Lamm M, Strober W, Bienenstock R, Mcghee JR, Mayer L (eds) Mucosal immunology, 3rd edn. Elsevier Academic, Boston, pp 1647–1660

    Chapter  Google Scholar 

  • Anderson DJ, Marathe J, Pudney J (2014) The structure of the human vaginal stratum corneum and its role in immune defense. Am J Reprod Immunol 71:618–623

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Barnhart KT, Pretorius ES, Timbers K, Shera D, Shabbout M, Malamud D (2004) In vivo distribution of a vaginal gel: MRI evaluation of the effects of gel volume, time and simulated intercourse. Contraception 70:498–505

    Article  CAS  PubMed  Google Scholar 

  • Barnhart KT, Pretorius ES, Shaunik A, Timbers K, Nasution M, Mauck C (2005) Vaginal distribution of two volumes of the novel microbicide gel cellulose sulfate (2.5 and 3.5mL). Contraception 72:65–70

    Article  CAS  PubMed  Google Scholar 

  • Bedford JM (2015) The functions – or not – of seminal plasma? Biol Reprod 92:18

    Article  PubMed  Google Scholar 

  • Brown J, Hooper G, Kenyon CJ, Haines S, Burt J, Humphries JM, Newman SP, Davis SS, Sparrow RA, Wilding IR (1997) Spreading and retention of vaginal formulations in post-menopausal women as assessed by gamma scintigraphy. Pharm Res 14:1073–1078

    Article  CAS  PubMed  Google Scholar 

  • Burden HP, Holmes CH, Persad R, Whittington K (2006) Prostasomes—their effects on human male reproduction and fertility. Hum Reprod Update 12:283–292

    Article  CAS  PubMed  Google Scholar 

  • Cadavid JA, Alvarez A, Markert UR, Cardona Maya W (2014) Differential protein expression in seminal plasma from fertile and infertile males. J Hum Reprod Sci 7:206–211

    Article  CAS  Google Scholar 

  • Chatterton BE, Penglis S, Kovacs JC, Presnell B, Hunt B (2004) Retention and distribution of two 99mTc-DTPA labelled vaginal dosage forms. Int J Pharm 271:137–143

    Article  CAS  PubMed  Google Scholar 

  • Cone RA (2009) Barrier properties of mucus. Adv Drug Deliv Rev 61:75–85

    Article  CAS  PubMed  Google Scholar 

  • Crawford G, Ray A, Gudi A, Shah A, Homburg R (2015) The role of seminal plasma for improved outcomes during in vitro fertilization treatment: review of the literature and meta-analysis. Hum Reprod Update 21:275–284

    Article  PubMed  Google Scholar 

  • Dahl M, Perin TL, Djurisic S, Rasmussen M, Ohlsson J, Buus S, Lindhard A, Hviid TV (2014) Soluble human leukocyte antigen-G in seminal plasma is associated with HLA-G genotype: possible implications for fertility success. Am J Reprod Immunol 72:89–105

    Article  CAS  PubMed  Google Scholar 

  • Doncel GF, Anderson S, Zalenskaya I (2014) Role of semen in modulating the female genital tract microenvironment—implications for HIV transmission. Am J Reprod Immunol 71:564–574

    Article  CAS  PubMed  Google Scholar 

  • Fichorova RN, Anderson DJ (1999) Differential expression of immunobiological mediators by immortalized human cervical and vaginal epithelial cells. Biol Reprod 60:508–514

    Article  CAS  PubMed  Google Scholar 

  • Fry TJ, Mackall CL (2005) The many faces of IL-7: from lymphopoiesis to peripheral T cell maintenance. J Immunol 174:6571–6576

    Article  CAS  PubMed  Google Scholar 

  • Gerozissis K, Jouannet P, Soufir JC, Dray F (1982) Origin of prostaglandins in human semen. J Reprod Fertil 65:401–404

    Article  CAS  PubMed  Google Scholar 

  • Gipson IK, Ho SB, Spurr-Michaud SJ, Tisdale AS, Zhan Q, Torlakovic E, Pudney J, Anderson DJ, Toribara NW, Hill JA 3rd (1997) Mucin genes expressed by human female reproductive tract epithelia. Biol Reprod 56:999–1011

    Article  CAS  PubMed  Google Scholar 

  • Gorelik L, Flavell RA (2002) Transforming growth factor-beta in T-cell biology. Nat Rev Immunol 2:46–53

    Article  CAS  PubMed  Google Scholar 

  • Graves HC, Sensabaugh GF, Blake ET (1985) Postcoital detection of a male-specific semen protein. Application to the investigation of rape. N Engl J Med 312:338–343

    Article  CAS  PubMed  Google Scholar 

  • Harrison OJ, Powrie FM (2013) Regulatory T cells and immune tolerance in the intestine. Cold Spring Harb Perspect Biol 5:a018341. doi:10.1101/cshperspect.a018341

    Article  PubMed Central  PubMed  Google Scholar 

  • Hill JA (1995) T-helper 1-type immunity to trophoblast: evidence for a new immunological mechanism for recurrent abortion in women. Hum Reprod 10(Suppl 2):114–120

    Article  CAS  PubMed  Google Scholar 

  • Kelley RW (1981) Prostaglandin synthesis in the male and female reproductive tract. J Reprod Fertil 62:293–304

    Article  Google Scholar 

  • Kokcu A, Yavuz E, Celik H, Bildircin D (2012) A panoramic view to relationships between reproductive failure and immunological factors. Arch Gynecol Obstet 286:1283–1289

    Article  CAS  PubMed  Google Scholar 

  • Kulkarni AB, Huh CG, Becker D, Geiser A, Lyght M, Flanders KC, Roberts AB, Sporn MB, Ward JM, Karlsson S (1993) Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc Natl Acad Sci USA 90:770–774

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kunz G, Beil D, Deininger H, Wildt L, Leyendecker G (1996) The dynamics of rapid sperm transport through the female genital tract: evidence from vaginal sonography of uterine peristalsis and hysterosalpingoscintigraphy. Hum Reprod 11:627–632

    Article  CAS  PubMed  Google Scholar 

  • Li J, Liu K, Liu Y, Xu Y, Zhang F, Yang H, Liu J, Pan T, Chen J, Wu M, Zhou X, Yuan Z (2013) Exosomes mediate the cell-to-cell transmission of IFN-alpha-induced antiviral activity. Nat Immunol 14:793–803

    Article  CAS  PubMed  Google Scholar 

  • Louissaint NA, Fuchs EJ, Bakshi RP, Nimmagadda S, Du Y, Macura KJ, King KE, Wahl R, Goldsmith AJ, Caffo B, Cao YJ, Anderson J, Hendrix CW (2012) Distribution of cell-free and cell-associated HIV surrogates in the female genital tract after simulated vaginal intercourse.J Infect Dis 205:725–732

    Article  CAS  PubMed  Google Scholar 

  • Macaluso M, Lawson L, Akers R, Valappil T, Hammond K, Blackwell R, Hortin G (1999) Prostate-specific antigen in vaginal fluid as a biologic marker of condom failure. Contraception 59:195–201

    Article  CAS  PubMed  Google Scholar 

  • Madison MN, Roller RJ, Okeoma CM (2014) Human semen contains exosomes with potent anti-HIV-1 activity. Retrovirology 11:102

    Article  PubMed Central  PubMed  Google Scholar 

  • Mann T (1954) The biochemistry of semen. Methuen, London

    Book  Google Scholar 

  • Marie JC, Liggitt D, Rudensky AY (2006) Cellular mechanisms of fatal early-onset autoimmunity in mice with the T cell-specific targeting of transforming growth factor-beta receptor. Immunity 25:441–454

    Article  CAS  PubMed  Google Scholar 

  • Mauck CK, Katz D, Sandefer EP, Nasution MD, Henderson M, Digenis GA, Su I, Page R, Barnhart K (2008) Vaginal distribution of Replens and K-Y Jelly using three imaging techniques. Contraception 77:195–204

    Article  PubMed  Google Scholar 

  • Mayer KH, Venkatesh KK (2011) Interactions of HIV, other sexually transmitted diseases, and genital tract inflammation facilitating local pathogen transmission and acquisition. Am J Reprod Immunol 65:308–316

    Article  PubMed Central  PubMed  Google Scholar 

  • Muranishi S, Yamamoto A, Okada H (1993) Rectal and vaginal absorption of peptides and proteins. Pharm Biotech 4:199–227

    Article  CAS  Google Scholar 

  • Norton EJ, Diekman AB, Westbrook VA, Mullins DW, Klotz KL, Gilmer LL, Thomas TS, Wright DC, Brisker J, Engelhard VH, Flickinger CJ, Herr JC (2002) A male genital tract-specific carbohydrate epitope on human CD52: implications for immunocontraception. Tissue Antigens 60:354–364

    Article  CAS  PubMed  Google Scholar 

  • Novy MJ, Eschenbach DA, Witken SS (2008) Infections as a cause of infertility. Global Library of Women’s Medicine. doi:10.3843/GLOWM.10328, ISSN 1756-2228

  • Oh SA, Li MO (2013) TGF-beta: guardian of T cell function. J Immunol 191:3973–3979

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pandya IJ, Cohen J (1985) The leukocytic reaction of the human uterine cervix to spermatozoa. Fertil Steril 43:417–421

    CAS  PubMed  Google Scholar 

  • Pannek J, Berges RR, Sauvageot J, Lecksell KL, Epstein JI, Partin AW (1999) Cell turnover in human seminal vesicles and the prostate: an immunohistochemical study. Prostate Cancer Prostatic Dis 2:200–203

    Article  PubMed  Google Scholar 

  • Politch JA, Tucker L, Bowman FP, Anderson DJ (2007) Concentrations and significance of cytokines and other immunologic factors in semen of healthy fertile men. Hum Reprod 22:2928–2935

    Article  CAS  PubMed  Google Scholar 

  • Pudney J, Anderson D (2011) Innate and acquired immunity in the human penile urethra. J Reprod Immunol 88:219–227

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pudney J, Quayle AJ, Anderson DJ (2005) Immunological microenvironments in the human vagina and cervix: mediators of cellular immunity are concentrated in the cervical transformation zone. Biol Reprod 73:1253–1263

    Article  CAS  PubMed  Google Scholar 

  • Quayle AJ, Kelly RW, Hargreave TB, James K (1989) Immunosuppression by seminal prostaglandins. Clin Exp Immunol 75:387–391

    CAS  PubMed Central  PubMed  Google Scholar 

  • Raghupathy R (1997) Th1-type immunity is incompatible with successful pregnancy. Immunol Today 18:478–482

    Article  CAS  PubMed  Google Scholar 

  • Rajagopalan S, Bryceson YT, Kuppusamy SP, Geraghty DE, Van Der Meer A, Joosten I, Long EO (2006) Activation of NK cells by an endocytosed receptor for soluble HLA-G. PLoS Biol 4:e9

    Article  PubMed Central  PubMed  Google Scholar 

  • Rametse CL, Olivier AJ, Masson L, Barnabas S, Mckinnon LR, Ngcapu S, Liebenberg LJ, Jaumdally SZ, Gray CM, Jaspan HB, Passmore JA (2014) Role of semen in altering the balance between inflammation and tolerance in the female genital tract: does it contribute to HIV risk? Viral Immunol 27:200–206

    Article  CAS  PubMed  Google Scholar 

  • Robertson SA, Ingman WV, O’leary S, Sharkey DJ, Tremellen KP (2002) Transforming growth factor beta–a mediator of immune deviation in seminal plasma. J Reprod Immunol 57:109–128

    Article  CAS  PubMed  Google Scholar 

  • Robertson SA, Prins JR, Sharkey DJ, Moldenhauer LM (2013) Seminal fluid and the generation of regulatory T cells for embryo implantation. Am J Reprod Immunol 69:315–330

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez-Martinez H, Kvist U, Ernerudh J, Sanz L, Calvete JJ (2011) Seminal plasma proteins: what role do they play? Am J Reprod Immunol 66(Suppl 1):11–22

    Article  PubMed  Google Scholar 

  • Sharkey DJ, Macpherson AM, Tremellen KP, Robertson SA (2007) Seminal plasma differentially regulates inflammatory cytokine gene expression in human cervical and vaginal epithelial cells. Mol Hum Reprod 13:491–501

    Article  CAS  PubMed  Google Scholar 

  • Sharkey DJ, Macpherson AM, Tremellen KP, Mottershead DG, Gilchrist RB, Robertson SA (2012a) TGF-beta mediates proinflammatory seminal fluid signaling in human cervical epithelial cells. J Immunol 189:1024–1035

    Article  CAS  PubMed  Google Scholar 

  • Sharkey DJ, Tremellen KP, Jasper MJ, Gemzell-Danielsson K, Robertson SA (2012b) Seminal fluid induces leukocyte recruitment and cytokine and chemokine mRNA expression in the human cervix after coitus. J Immunol 188:2445–2454

    Article  CAS  PubMed  Google Scholar 

  • Shull MM, Ormsby I, Kier AB, Pawlowski S, Diebold RJ, Yin M, Allen R, Sidman C, Proetzel G, Calvin D et al (1992) Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 359:693–699

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Templeton AA, Cooper I, Kelly RW (1978) Prostaglandin concentrations in the semen of fertile men. J Reprod Fertil 52:147–150

    Article  CAS  PubMed  Google Scholar 

  • Thompson LA, Barratt CL, Bolton AE, Cooke ID (1992) The leukocytic reaction of the human uterine cervix. Am J Reprod Immunol 28:85–89

    Article  CAS  PubMed  Google Scholar 

  • Venter PF, Iturralde M (1979) Migration of a particulate radioactive tracer from the vagina to the peritoneal cavity and ovaries. S Afr Med J 55:917–919

    CAS  PubMed  Google Scholar 

  • Vojtech L, Woo S, Hughes S, Levy C, Ballweber L, Sauteraud RP, Strobl J, Westerberg K, Gottardo R, Tewari M, Hladik F (2014) Exosomes in human semen carry a distinctive repertoire of small non-coding RNAs with potential regulatory functions. Nucleic Acids Res 42:7290–7304

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wahl SM, Wen J, Moutsopoulos N (2006) TGF-beta: a mobile purveyor of immune privilege. Immunol Rev 213:213–227

    Article  CAS  PubMed  Google Scholar 

  • Zamboni L (1972) Fertilization in the mouse. In: Moghissi KS, Hafez ESE (eds) Biology of mammalian fertilization and Implantation. C. C. Thomas, Springfield, IL

    Google Scholar 

  • Zervomanolakis I, Ott HW, Hadziomerovic D, Mattle V, Seeber BE, Virgolini I, Heute D, Kissler S, Leyendecker G, Wildt L (2007) Physiology of upward transport in the human female genital tract. Ann N Y Acad Sci 1101:1–20

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

Supported by NIH grant U19AI096398 (DJA).

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Correspondence to Deborah J. Anderson Ph.D. .

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Anderson, D.J., Politch, J.A. (2015). Role of Seminal Plasma in Human Female Reproductive Failure: Immunomodulation, Inflammation, and Infections. In: Bronson, R. (eds) The Male Role in Pregnancy Loss and Embryo Implantation Failure. Advances in Experimental Medicine and Biology, vol 868. Springer, Cham. https://doi.org/10.1007/978-3-319-18881-2_7

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