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Seminal plasma as a diagnostic fluid for male reproductive system disorders

Key Points

  • Seminal plasma contains a large number of tissue-specific proteins secreted by individual organs of the male reproductive system

  • Male reproductive system disorders result in altered composition of the seminal plasma proteome

  • High concentrations of organ-specific proteins enable their accurate quantification by mass spectrometry, facilitating biomarker discovery

  • As well as being a promising biological fluid for biomarker discovery, seminal plasma might find a unique niche as a clinical diagnostic fluid

  • Because cancer-specific proteins can appear earlier in seminal plasma than in blood serum, seminal plasma could facilitate the early diagnosis of prostate and testicular cancers

Abstract

Molecular biomarkers hold promise to advance the noninvasive diagnosis of male reproductive system disorders and facilitate the identification and management of these conditions through screening, early diagnosis and more accurate prognosis. Seminal plasma has great potential as a proximal fluid for protein biomarker discovery and as a clinical sample for noninvasive diagnostics. The seminal plasma proteome contains thousands of proteins and includes a large number of tissue-specific proteins that might accurately indicate a pathological process in the tissue of origin. Potential protein biomarkers for male reproductive system disorders are more abundant in seminal plasma than in blood serum or urine, and, therefore, are more easily identified and quantified in semen by mass spectrometry and other techniques. These methods have enabled elaboration of the composition of the seminal plasma proteome and the tissue specificity of seminal plasma proteins. Strategies have been developed to discover protein biomarkers in seminal plasma through integrated 'omics' approaches. Biomarkers of male infertility and prostate cancer are now emerging, and it is evident that seminal plasma has the potential to complement other diagnostic tools available in urology clinics.

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Figure 1: Male reproductive system contributions to seminal plasma, and methods to collect enriched fluids.
Figure 2: Approaches to identify low-abundance proteins in seminal plasma.
Figure 3: Tissue-specific genes and proteins.
Figure 4: Differential diagnosis of azoospermia (obstructive versus nonobstructive) and prediction of subtypes of nonobstructive azoospermia with proteomic biomarkers ECM1 and TEX101 measured in seminal plasma.
Figure 5: Biomarker discovery in seminal plasma through integration of 'omics' technologies.

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Acknowledgements

We thank A. Dimitromanolakis and N. Musrap for help with the preparation of figures. The work of the authors was funded by grants from the Canadian Institutes of Health Research (CIHR) and Physician's Services Incorporated. A.P.D. was supported by CIHR and Mount Sinai Hospital Foundation Norm Hollend Post-Doctoral Fellowships.

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A.P.D. researched data for the article. A.P.D., K.J. and E.P.D. made substantial contributions to the discussion of content. A.P.D. and P.S. contributed to writing the article, and all authors contributed to review and editing of the manuscript before submission.

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Correspondence to Eleftherios P. Diamandis.

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A.P.D., K.J. and E.P.D. have applied for a patent titled “Markers of the male urogenital tract,” international PCT application WO/2012/021969. P.S. declares no competing interests.

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Drabovich, A., Saraon, P., Jarvi, K. et al. Seminal plasma as a diagnostic fluid for male reproductive system disorders. Nat Rev Urol 11, 278–288 (2014). https://doi.org/10.1038/nrurol.2014.74

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