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.
Similar content being viewed by others
References
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.
Finer LB, Zolna MR. Unintended pregnancy in the United States: incidence and disparities, 2006. Contraception. 2011;84(5):478–485.
Winner B, Peipert JF, Zhao Q, et al. Effectiveness of long-acting reversible contraception. N Engl J Med. 2012;366(21):1998–2007.
Florman HM, Ducibella T. Knobil and Neill’s Physiology of Reproduction. Amsterdam, the Netherlands; Boston, MA: Elsevier, c2006; 2006.
Li L, Zheng P, Dean J. Maternal control of early mouse development. Development. 2010;137(6):859–870.
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.
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.
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.
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.
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.
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.
Harlow E, Lane D. Antibodies a Laboratory Manual. NY: Cold Spring Harbor; 1988.
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.
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.
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.
World Health Organization DoRHaR. WHO Laboratory Manual for the Examination of Semen and Sperm–Cervical Mucus Interaction. 4th ed. Cambridge: Cambridge University Press; 1999.
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.
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.
Tukey JW. Exploratory Data Analysis. Boston, MA: Addison-Wesley; 1977.
Rousseeuw PJ, Ruts I, Tukey JW. The Bagplot: A Bivariate Boxplot. Am Stat. 1999;53(4):382–387. JSTOR 2686061.
Chamley LW, Clarke GN. Antisperm antibodies and conception. Semin Immunopathol. 2007;29(2):169–184.
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.
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.
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.
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.
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.
Buffone MG, Foster JA, Gerton GL. The role of the acrosomal matrix in fertilization. Int J Dev Biol. 2008;52(5–6):511–522.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Sehgal S, Gupta SK, Bhatnagar P. Long-term effects of immunization with porcine zona pellucida on rabbit ovaries. Pathology. 1989;21(2):105–110.
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.
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.
Fayrer Hosken RA, Dookwah HD, Brandon CI. Immunocontrol in dogs. Animal Reprod Sci. 2000;60–61:365–373.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Published:
Issue Date:
DOI: https://doi.org/10.1177/1933719114542009