Abstract
Sperm competence in animal fertilization requires the collective activities of numerous sperm-specific proteins that are typically alloimmunogenic in females. Consequently, sperm membrane alloantigens are potential targets for contraceptives that act by blocking the proteins’ functions in gamete interactions. Here we used a targeted proteomics approach to identify the major alloantigens in swine sperm membranes and lipid rafts, and thereby systematically defined the repertoire of these sperm-specific proteins in a single species. Gilts with high alloantibody reactivity to proteins in sperm membranes or lipid rafts produced fewer offspring (73% decrease) than adjuvant-only or nonimmune control animals. Alloantisera recognized more than 20 potentially unique sperm membrane proteins and five sperm lipid raft proteins resolved on two-dimensional immunoblots with or without prior enrichment by anion exchange chromatography. Dominant sperm membrane alloantigens identified by mass spectrometry included the ADAMs fertilin α, fertilin ß, and cyritestin. Less abundant alloantigens included ATP synthase F1 β subunit, myo-inositol monophosphatase-1, and zymogen granule membrane glycoprotein-2. Immunodominant sperm lipid raft alloantigens included SAMP14, lymphocyte antigen 6K, and the epididymal sperm protein E12. Of the fifteen unique membrane alloantigens identified, eleven were known sperm-specific proteins with uncertain functions in fertilization, and four were not previously suspected to exist as sperm-specific isoforms. De novo sequences of tryptic peptides from sperm membrane alloantigen “M6” displayed no evident homology to known proteins, so is a newly discovered sperm-specific gene product in swine. We conclude that alloimmunizing gilts with sperm membranes or lipid rafts evokes formation of antibodies to a relatively small number of dominant alloantigens that include known and novel sperm-specific proteins with possible functions in fertilization and potential utility as targets for immunocontraception.
Highlights
Anti-fertility vaccines offer the promise of inexpensive, long-acting, non-hormonal control of reproduction in humans and in non-human pests from foxes to feral swine to elephants [1,2,3,4]
We found that the relatively small number (10–20 proteins) of dominant boar sperm membrane alloantigens (SMA) and sperm lipid raft alloantigens (SLRAs) includes suitable targets for swine immunocontraception, and comprises both known sperm-specific proteins as well as one new protein not represented in existing protein sequence databases
Despite limited protein yields of the other SLRA, we identified the two dominant alloantigens as ELSPBP1 and sperm acrosomal membrane protein 14 (SAMP14), both of which were detected as SMA in washed membranes
Summary
Anti-fertility vaccines offer the promise of inexpensive, long-acting, non-hormonal control of reproduction in humans and in non-human pests from foxes to feral swine to elephants [1,2,3,4]. Inadequate knowledge of target antigens’ immunogenicity and functions in fertilization have limited the effectiveness of sperm-based vaccines. Unique sets of sperm and egg proteins mediate the coordinated cellular events of fertilization [7,8]; many of these proteins are gamete specific, making them good candidate targets for immunocontraception. Unlike cellular and molecular processes in somatic tissues, fertilization events differ significantly among species [7], and individual sperm or egg proteins do not necessarily function identically in all species, especially if a process is mediated by gene family members with overlapping activities. A full understanding of mammalian fertilization, and in turn the rational formulation of immunocontraceptives, will require characterization in multiple animal species of all sperm and egg proteins that mediate its various events
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