Impact of semen-derived amyloid (SEVI) on sperm viability and motility: its implication in male reproductive fitness
Human semen contains a large number of macromolecules, including proteins/enzymes and carbohydrates, regulating and protecting sperm cells. Proteomic analysis of human seminal fluid led to the discovery of semen amyloids derived from short peptide fragments of the proteins prostatic acid phosphatase (PAP) and semenogelin (SG) which are known to play a crucial role in enhancing HIV infection. However, the relevance of their existence in human semen and role in maintaining sperm behavior remains unclear. Distinct physiological, biochemical, and biophysical attributes might cause these amyloids to influence sperm behavior positively or negatively, affecting fertilization or other reproductive processes. We assessed the direct effect of amyloids derived from a PAP248–286 fragment, on sperm motility and viability, which are crucial parameters for assessment of sperm quality in semen. Co-incubation of human sperm with PAP248–286 amyloids at normal physiological concentrations formed in buffer led to significant reduction in sperm viability, though approximately a 10× higher concentration was needed to show a similar effect with amyloid formed in seminal fluid. Both forms of PAP248–286 amyloid also had a significant impact on sperm motility at physiological levels, in agreement with a previous report. Our study suggests that PAP248–286 amyloids can directly influence sperm motility and viability in a concentration-dependent manner. We hypothesise that the direct toxic effect of PAP248–286 amyloid is normally mitigated by other seminal fluid ingredients, but that in pathological conditions, where PAP248–286 concentrations are elevated and it plays a role in determining sperm health and viability, with relevance for male fertility as well as sterility.
KeywordsSemen-derived amyloids PAP248–286 SEVI Male sterility
Prostatic acid phosphatase
Semen-derived enhancer of viral infection
Dulbecco’s phosphate buffer saline
Revolutions per minutes
Transmission electron microscope
Sperm motility index
Fluorescence-activated cell sorting
We are thankful to the technical staff of central instrument facility at RGCB, and KJK hospital Thiruvananthapuram, Kerala, India for their unconditional support. Mr. Vijay Kumar is thankful to the lab members of molecular reproduction at RGCB for their help during this project. Mr. Vijay Kumar acknowledges University Grants Commission, India and Social Justice and Empowerment Department, Govt. of India for RGN fellowship.
This study was partially supported by Department of Science and Technology, Government of India (Grant number SB/YS/LS-130/2013).
Compliance with ethical standards
Conflict of interest
The authors do not have any conflict of interest to declare.
- Barros C, Vigil P, Herrera E, Arguello B, Walker R (1984) Selection of morphologically abnormal sperm by human cervical mucus. Arch Androl 12:95–107Google Scholar
- Easterhoff D (2013) Characterization of amyloid fibrils in seminal fluid and their interaction with pathogens. University of Rochester, New YorkGoogle Scholar
- Elia J, Imbrogno N, Delfino M, Mazzilli R, Rossi T, Mazzilli F (2010) The importance of the sperm motility classes-future directions. Open Androl J 2:42–43Google Scholar
- Elias AK (2015) The functional studies of amyloid fibrils and their toxicity. Doctoral dissertationGoogle Scholar
- Hartjen P, Frerk S, Hauber I, Matzat V, Thomssen A, Holstermann B, Hohenberg H, Schulze W, Schulze Zur Wiesch J, van Lunzen J (2012a) Assessment of the range of the HIV-1 infectivity enhancing effect of individual human semen specimen and the range of inhibition by EGCG. AIDS Res Ther 9(1):2CrossRefGoogle Scholar
- Kim KA, Yolamanova M, Zirafi O, Roan NR, Staendker L, Forssmann WG, Burgener A, Dejucq-Rainsford N, Hahn BH, Shaw GM, Greene WC, Kirchhoff F, Munch J (2010) Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI. Retrovirology 7:55CrossRefGoogle Scholar
- Munch J, Rucker E, Standker L, Adermann K, Goffinet C, Schindler M, Wildum S, Chinnadurai R, Rajan D, Specht A, Gimenez-Gallego G, Sanchez PC, Fowler DM, Koulov A, Kelly JW, Mothes W, Grivel JC, Margolis L, Keppler OT, Forssmann WG, Kirchhoff F (2007) Semen-derived amyloid fibrils drastically enhance HIV infection. Cell 131(6):1059–1071CrossRefGoogle Scholar
- Roan NR, Liu H, Usmani SM, Neidleman J, Muller JA, Avila-Herrera A, Gawanbacht A, Zirafi O, Chu S, Dong M, Kumar ST, Smith JF, Pollard KS, Fandrich M, Kirchhoff F, Munch J, Witkowska HE, Greene WC (2014) Liquefaction of semen generates and later degrades a conserved semenogelin peptide that enhances HIV infection. J Virol 88(13):7221–7234CrossRefGoogle Scholar
- Roan NR, Sandi-Monroy N, Kohgadai N, Usmani SM, Hamil KG, Neidleman J, Montano M, Standker L, Rocker A, Cavrois M, Rosen J, Marson K, Smith JF, Pilcher CD, Gagsteiger F, Sakk O, O'Rand M, Lishko PV, Kirchhoff F, Munch J, Greene WC (2017) Semen amyloids participate in spermatozoa selection and clearance. eLife 6:e24888CrossRefGoogle Scholar
- Tasken K, Angelsen A, Svindland A, Eide T, Berge V, Wahlquist R, Karlsen S (2005) Markers for diagnosis, prediction and prognosis of prostate cancer. Tidsskrift for den Norske laegeforening: tidsskrift for praktisk medicin, ny raekke 125(23):3279–3282Google Scholar
- Usmani SM, Zirafi O, Muller JA, Sandi-Monroy NL, Yadav JK, Meier C, Weil T, Roan NR, Greene WC, Walther P, Nilsson KP, Hammarstrom P, Wetzel R, Pilcher CD, Gagsteiger F, Fandrich M, Kirchhoff F, Munch J (2014) Direct visualization of HIV-enhancing endogenous amyloid fibrils in human semen. Nat Commun 5:3508CrossRefGoogle Scholar
- Whelly S, Muthusubramanian A, Powell J, Johnson S, Hastert MC, Cornwall GA (2016) Cystatin-related epididymal spermatogenic subgroup members are part of an amyloid matrix and associated with extracellular vesicles in the mouse epididymal lumen. MHR Basic Sci Reprod Med 22(11):729–744CrossRefGoogle Scholar