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The Role of SPRASA in Female Fertility

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Abstract

Fertility is a complex process and infertility can have many causes. Sperm protein reactive with antisperm antibody (SPRASA)/sperm lysozyme-like protein 1 is a protein discovered as the target of autoantibodies in infertile men and previously thought to be expressed only in sperm. Using a bovine in vitro fertilization model, we have shown that SPRASA antiserum reduced sperm binding to zona-free oocytes and the development of embryos to morulae but did not affect the postfertilization cleavage rate to 2 cells or sperm motility. We demonstrated that SPRASA was expressed in ovarian follicles, corpora lutea, and oocytes by a combination of reverse transcription-polymerase chain reaction and immunohistochemistry. Female mice immunized with SPRASA had profound infertility following timed matings and those mice that did become pregnant had reduced fetal viability. The levels of antibodies reactive with SPRASA in 204 fertile and 202 infertile couples were elevated in 3 infertile but no fertile women. Together, these results indicate that SPRASA has a role in female fertility.

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References

  1. Thoma ME, McLain AC, Louis JF, et al. Prevalence of infertility in the United States as estimated by the current duration approach and a traditional constructed approach. Fertil Steril. 2013;99(5):1324–1331 e1321.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Finer LB, Zolna MR. Unintended pregnancy in the United States: incidence and disparities, 2006. Contraception. 2011;84(5):478–485.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Winner B, Peipert JF, Zhao Q, et al. Effectiveness of long-acting reversible contraception. N Engl J Med. 2012;366(21):1998–2007.

    Article  CAS  PubMed  Google Scholar 

  4. Florman HM, Ducibella T. Knobil and Neill’s Physiology of Reproduction. Amsterdam, the Netherlands; Boston, MA: Elsevier, c2006; 2006.

    Google Scholar 

  5. Li L, Zheng P, Dean J. Maternal control of early mouse development. Development. 2010;137(6):859–870.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mandal A, Klotz KL, Shetty J, et al. SLLP1, a unique, intraacrosomal, non-bacteriolytic, c lysozyme-like protein of human spermatozoa. Biol Reprod. 2003;68(5):1525–1537.

    Article  CAS  PubMed  Google Scholar 

  7. Wang QT, Piotrowska K, Ciemerych MA, et al. A genome-wide study of gene activity reveals developmental signaling pathways in the preimplantation mouse embryo. Developmental Cell. 2004;6(1):133–144.

    Article  CAS  PubMed  Google Scholar 

  8. Chiu WW, Erikson EK, Sole CA, Shelling AN, Chamley LW. SPRASA, a novel sperm protein involved in immune-mediated infertility. Hum Reprod. 2004;19(2):243–249.

    Article  CAS  PubMed  Google Scholar 

  9. Herrero MB, Mandal A, Digilio LC, Coonrod SA, Maier B, Herr JC. Mouse SLLP1, a sperm lysozyme-like protein involved in spermegg binding and fertilization. Dev Biol. 2005;284(1):126–142.

    Article  CAS  PubMed  Google Scholar 

  10. Sachdev M, Mandal A, Mulders S, et al. Oocyte specific oolemmal SAS1B involved in sperm binding through intra-acrosomal SLLP1 during fertilization. Dev Biol. 2012;363(1):40–51.

    Article  CAS  PubMed  Google Scholar 

  11. Naz RK, Dhandapani L. Identification of human sperm proteins that interact with human zona pellucida3 (ZP3) using yeast two-hybrid system. J Reprod Immunol. 2010;84(1):24–31.

    Article  CAS  PubMed  Google Scholar 

  12. Harlow E, Lane D. Antibodies a Laboratory Manual. NY: Cold Spring Harbor; 1988.

    Google Scholar 

  13. Schurmann A, Wells DN, Oback B. Early zygotes are suitable recipients for bovine somatic nuclear transfer and result in cloned offspring. Reproduction. 2006;132(6):839–848.

    Article  CAS  PubMed  Google Scholar 

  14. Grant VJ, Irwin RJ, Standley NT, Shelling AN, Chamley LW. Sex of bovine embryos may be related to mothers’ preovulatory follicular testosterone. Biol Reprod. 2008;78(5):812–815.

    Article  CAS  PubMed  Google Scholar 

  15. Lee CY, Khorasani AM, Dorjee S. Assessment of progesteroneinduced acrosome reaction by biotinylated monoclonal antibody probes. Am J Reprod Immunol. 1998;39(3):164–171.

    Article  CAS  PubMed  Google Scholar 

  16. World Health Organization DoRHaR. WHO Laboratory Manual for the Examination of Semen and Sperm–Cervical Mucus Interaction. 4th ed. Cambridge: Cambridge University Press; 1999.

    Google Scholar 

  17. Myers M, Britt KL, Wreford NG, Ebling FJ, Kerr JB. Methods for quantifying follicular numbers within the mouse ovary. Reproduction. 2004;127(5):569–580.

    Article  CAS  PubMed  Google Scholar 

  18. Fischer AH, Jacobson KA, Rose J, Zeller R. Hematoxylin and eosin staining of tissue and cell sections. Cold Spring Harbor Protocols. 2008;3(5):1–2.

    Google Scholar 

  19. Tukey JW. Exploratory Data Analysis. Boston, MA: Addison-Wesley; 1977.

    Google Scholar 

  20. Rousseeuw PJ, Ruts I, Tukey JW. The Bagplot: A Bivariate Boxplot. Am Stat. 1999;53(4):382–387. JSTOR 2686061.

    Google Scholar 

  21. Chamley LW, Clarke GN. Antisperm antibodies and conception. Semin Immunopathol. 2007;29(2):169–184.

    Article  CAS  PubMed  Google Scholar 

  22. Inoue N, Ikawa M, Isotani A, Okabe M. The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs. Nature. 2005;434(7030):234–238.

    Article  CAS  PubMed  Google Scholar 

  23. Saxena DK, Tanii I, Oh-oka T, Yoshinaga K, Toshimori K. Behaviour and role of an intra-acrosomal antigenic molecule, acrin 3, during mouse fertilisation in vitro. Zygote. 2000;8(4):329–338.

    Article  CAS  PubMed  Google Scholar 

  24. Coonrod SA, Herr JC, Westhusin ME. Inhibition of bovine fertilization in vitro by antibodies to SP-10. J Reprod Fertil. 1996;107(2):287–297.

    Article  CAS  PubMed  Google Scholar 

  25. Okabe M, Adachi T, Takada K, et al. Capacitation-related changes in antigen distribution on mouse sperm heads and its relation to fertilization rate in vitro. J Reprod Immunol. 1987;11(2):91–100.

    Article  CAS  PubMed  Google Scholar 

  26. Primakoff P, Hyatt H, Myles DG. A role for the migrating sperm surface antigen PH-20 in guinea pig sperm binding to the egg zona pellucida. J Cell Biol. 1985;101(6):2239–2244.

    Article  CAS  PubMed  Google Scholar 

  27. Buffone MG, Foster JA, Gerton GL. The role of the acrosomal matrix in fertilization. Int J Dev Biol. 2008;52(5–6):511–522.

    Article  PubMed  Google Scholar 

  28. Howes E, Pascall JC, Engel W, Jones R. Interactions between mouse ZP2 glycoprotein and proacrosin; a mechanism for secondary binding of sperm to the zona pellucida during fertilization. J Cell Sci. 2001;114(pt 22):4127–4136.

    CAS  PubMed  Google Scholar 

  29. Saxena DK, Tanii I, Yoshinaga K, Toshimori K. Role of intraacrosomal antigenic molecules acrin 1 (MN7) and acrin 2 (MC41) in penetration of the zona pellucida in fertilization in mice. J Reprod Fertil. 1999;117(1):17–25.

    Article  CAS  PubMed  Google Scholar 

  30. Auer J, Camoin L, Courtot AM, Hotellier F, De Almeida M. Evidence that P36, a human sperm acrosomal antigen involved in the fertilization process is triosephosphate isomerase. Mol Reprod Dev. 2004;68(4):515–523.

    Article  CAS  PubMed  Google Scholar 

  31. Prendergast DW, Woad KJ, Chamley LW, Shelling AN. Spatial and temporal expression of the sperm protein SPRASA in mice. Biol Reprod. 2008;78(301):74a.

    Google Scholar 

  32. Ekhlasi-Hundrieser M, Sinowatz F, Greiser De Wilke I, Waberski D, Topfer-Petersen E. Expression of spermadhesin genes in porcine male and female reproductive tracts. Mol Reprod Dev. 2002;61(1):32–41.

    Article  CAS  PubMed  Google Scholar 

  33. Zhang H, Martin-DeLeon PA. Mouse Spam1 (PH-20) is a multifunctional protein: evidence for its expression in the female reproductive tract. Biol Reprod. 2003;69(2):446–454.

    Article  CAS  PubMed  Google Scholar 

  34. Hao Z, Wolkowicz MJ, Shetty J, et al. SAMP32, a testis-specific, isoantigenic sperm acrosomal membrane-associated protein. Biol Reprod. 2002;66(3):735–744.

    Article  CAS  PubMed  Google Scholar 

  35. Hamatani T, Carter MG, Sharov AA, Ko MS. Dynamics of global gene expression changes during mouse preimplantation development. Dev Cell. 2004;6(1):117–131.

    Article  CAS  PubMed  Google Scholar 

  36. Wood DM, Dunbar BS. Direct detection of two cross-reactive antigens between porcine and rabbit zonae pellucidae by radioimmunoassay and immunoelectrophoresis. J Exp Zool. 1981;217(3):423–433.

    Article  CAS  PubMed  Google Scholar 

  37. Skinner SM, Mills T, Kirchick HJ, Dunbar BS. Immunization with zona pellucida proteins results in abnormal ovarian follicular differentiation and inhibition of gonadotropin-induced steroid secretion. Endocrinology. 1984;115(6):2418–2432.

    Article  CAS  PubMed  Google Scholar 

  38. Mahi Brown CA, Yanagimachi R, Hoffman JC, Huang TT Jr. Fertility control in the bitch by active immunization with porcine zonae pellucidae: use of different adjuvants and patterns of estradiol and progesterone levels in estrous cycles. Biol Reprod. 1985;32(4):761–772.

    Article  CAS  PubMed  Google Scholar 

  39. Mahi-Brown CA, Yanagimachi R, Nelson ML, Yanagimachi H, Palumbo N. Ovarian histopathology of bitches immunized with porcine zonae pellucidae. Am J Reprod Immunol Microbiol. 1988;18(3):94–103.

    Article  CAS  PubMed  Google Scholar 

  40. Sacco AG, Yurewicz EC, Subramanian MG. Effect of varying dosages and adjuvants on antibody response in squirrel monkeys (Saimiri sciureus) immunized with the porcine zona pellucida Mr = 55,000 glycoprotein (ZP3). Am J Reprod Immunol. 1989;21(1):1–8.

    Article  CAS  PubMed  Google Scholar 

  41. Sehgal S, Gupta SK, Bhatnagar P. Long-term effects of immunization with porcine zona pellucida on rabbit ovaries. Pathology. 1989;21(2):105–110.

    Article  CAS  PubMed  Google Scholar 

  42. Upadhyay SN, Thillaikoothan P, Bamezai A, Jayaraman S, Talwar GP. Role of adjuvants in inhibitory influence of immunization with porcine zona pellucida antigen (ZP-3) on ovarian folliculogenesis in bonnet monkeys: a morphological study. Biol Reprod. 1989;41(4):665–673.

    Article  CAS  PubMed  Google Scholar 

  43. Hasegawa A, Koyama K, Inoue M, Takemura T, Isojima S. Antifertility effect of active immunization with ZP4 glycoprotein family of porcine zona pellucida in hamsters. J Reprod Immunol. 1992;22(2):197–210.

    Article  CAS  PubMed  Google Scholar 

  44. Fayrer Hosken RA, Dookwah HD, Brandon CI. Immunocontrol in dogs. Animal Reprod Sci. 2000;60–61:365–373.

    Article  CAS  Google Scholar 

  45. Wood DM, Liu C, Dunbar BS. Effect of alloimmunization and heteroimmunization with zonae pellucidae on fertility in rabbits. Biol Reprod. 1981;25(2):439–450.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Olivia J. Holland PhD.

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Wagner, A., Holland, O.J., Tong, M. et al. The Role of SPRASA in Female Fertility. Reprod. Sci. 22, 452–461 (2015). https://doi.org/10.1177/1933719114542009

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