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Abstract Background The ‘omics’ approach for a noninvasive diagnosis of male reproductive system disorders has gained momentum during the last decade, particularly from a screening and prognosis point of view. Due to the rapid development in assisted reproductive technologies (ART) over the years, the major focus of proteomic studies has been around the ejaculated spermatozoa. Although seminal plasma is not a requirement for ART, the question arose whether the role of seminal plasma is merely to transport spermatozoa. Main body Seminal plasma (SP) contains a large diversity of proteins that are essential not only for sperm transport, but also for sperm protection and maturation. Most of the proteins bind to sperm surface through exosomes (epididymosomes and prostasomes), modulating sperm function, interaction with the female reproductive tract and finally fertilization. This review focuses on the state-of-art discoveries regarding SP proteome and its role in fertilization. Conclusion Tissue-specific proteins in the SP have emerged as fundamental contributors for protein biomarker discovery. This is important for a noninvasive diagnosis of male infertility and development of new therapeutic approaches. Moreover, ART success rates may be improved by taking into account the critical role of seminal proteome in fertilization.

Autoantibody production is one of the leading factors of immune infertility, an autoimmune disease of the male reproductive system. The potential involvement of MHC-class II derived self-peptides against bacterial proteins in the antisperm antibody (ASA) production has been reported previously. Apparently, Streptococcus agalactiae has been considered as an important pathogen to impart infection-induced infertility in a bacteriospermia associated leukocytospermia (LCS/BS) state. Hence, the present study attempts to confirm S. agalactiae specific Laminin binding protein (Lmb) derived self-peptide (‘KDSYTKKAKAFKKEA’) namely human Motile Sperm domain-containing protein 2 (MOSPD2) as an auto-antigen in LCS/BS condition. Semen samples were collected from infertile men with LCS/BS (n ​= ​17) and their fertile counterparts (n ​= ​10). Gram-positive bacteria were predominantly identified in the entire 17 LCS samples using culture method followed by 16S rDNA sequencing technique. TLRs 2 and 4 expression used as markers of immune response in spermatozoa and sperm dysfunction were elevated in the LCS/BS spermatozoa as compared to their fertile counterparts. A significant increase in oxidative stress indices i.e., protein carbonylation, lipid peroxidation and acridine orange test (AOT), was also observed in the LCS/BS spermatozoa. Spermatozoa lysate (both auto and heterologous), bacterial lysate (control) and synthesized MOSPD2 self-peptide were used to test their antigenicity against the autoantibodies by rocket immunoelectrophoresis (RIEP) assay. Seminal plasma from LCS/BS patients with S. agalactiae was used as the source of autoantibodies. Spermatozoa and bacteria lysate; and MOSPD2 self-peptide were able to bind autoantibodies in the seminal plasma. Besides, the self-peptide showed a dose dependent increase in the precipitation of antibody. T-cell epitope mapping of 48 Enterococcus faecalis and 91Staphylococcus aureus surface proteins confirmed MOSPD2 as a global auto-antigen. Thus, augmentation of TLR expression in LCS/BS spermatozoa inferred MOSPD2 to be a putative immunogen. Altogether, these findings will delineate the significance of MOSPD2 auto-antigen in a bacteria derived immune infertility condition. Keywords: Auto-antigen, Auto-antibody, Immune infertility, Laminin binding protein, Motile sperm domain-containing protein 2