Sperm proteomics: fertility diagnostic testing beyond the semen analysis?

REFLECTIONS Sperm proteomics: fertility diagnostic testing beyond the semen analysis? Proteome refers to the complement of proteins produced by an organism or biologic system (1). These proteins can change with time due to internal physiologic requirements or environmental stressors. Proteomics refers to the study of these protein changes to gain a better understanding of the underlying cellular processes within the organism or biologic system. The study by Pilatz et al. (2) provides a vision into sperm proteomics within an inflammatory environment caused by epididymitis. Epididymitis occurs most commonly during the prime reproductive years of men between the ages of 19 and 35 years (3). Even with adequate treatment and resolution of symptoms associated with the infection, the detrimental effects may persist on a subclinical level despite a normal semen analysis. Urogenital infections are known to cause male infertility in up to 8% of men (4). The study by Pilatz et al. (2) demonstrates the effects of epididymitis on spermatogenesis as reflected by the changes in sperm parameters and sperm protein composition or proteomics by comparing different changes between men with epididymitis and healthy controls. This study highlights several important points. First, semen analysis alone may not be enough to diagnose infertility after epididymitis. Up to 60% of men will have a normal semen analysis after an episode of acute epididymitis. For those with an abnormal semen analysis, this may persist even after adequate antibiotic treatment and resolution of symptoms (2). This may be, in part, due to elevated levels of oxidative stress, as studied by Sharma et al. (5). Second, the ability to evaluate infertility, which may be lacking in traditional semen analysis, may reside in studying sperm proteomic markers. Many of the proteins evaluated after epididymitis were found to be down-regulated and have been found to be associated with reduced sperm function, subfertility and infertility, and epididymal dysfunction (2). The same may also be found in serum markers as well. Third, additional larger cohort studies or a multicenter pooled cohort analysis will have to be performed to further validate the results of these and previous studies. Despite clearly demonstrating the down-regulation of 35 sperm proteins from patients with epididymitis compared with controls, the study was small (N ¼ 8) and the protein concentration was low, necessitating pooling of the semen samples in the study cohort along with the healthy controls (N ¼ 10).

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Because the semen analysis is one of the major cornerstones in fertility evaluation, this study emphasizes the importance of additional testing needed to fully characterize the effects of infection and inflammation on male fertility. Proteomics may be the answer that we have been searching for to advance our evaluation and understanding of male infertility. We have been reliant on a good but imperfect test in the semen analysis for far too long due to a lack of better noninvasive testing. Proteomics provides the next step in dramatically improving our diagnostic armamentarium in accurately providing couples with fertility counseling and treatment recommendations. Further studies in this promising arena may reveal additional therapeutic areas that male fertility specialists can treat in the near future. Edmund Y. Ko, M.D. Department of Urology, Loma Linda University School of Medicine, Loma Linda, California http://dx.doi.org/10.1016/j.fertnstert.2014.04.011 You can discuss this article with its authors and with other ASRM members at http://fertstertforum.com/koe-sperm-proteomicsfertility-diagnostic-testing/ Use your smartphone to scan this QR code and connect to the discussion forum for this article now.* * Download a free QR code scanner by searching for “QR scanner” in your smartphone’s app store or app marketplace.

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National Cancer Institute. What is cancer proteomics? Available at: http://pro teomics.cancer.gov/whatisproteomics. Accessed March 20, 2014. Pilatz A, Lochnit G, Karnati S, Paradowska-Dogan A, Lang T, Schultheiss D, et al. Acute epididymitis induces alterations in sperm protein composition. Fertil Steril 2014. Nickel JC. Prostatitis, and related conditions, orchitis, epididymitis. In: Wein AJ, editor. Campbell-Walsh urology. 10th ed. Philadelphia: Saunders Elsevier; 2011:354–6. Weidner W, Pilatz A, Diemer T, Schuppe HC, Rusz A, Wagenlehner F. Male urogenital infections: impact of infection and inflammation on ejaculate parameters. World J Urol 2013;31:717–23. Sharma R, Agarwal A, Mohanty G, du Plessis SS, Gopalan B, Willard B, et al. Proteomic analysis of seminal fluid from men exhibiting oxidative stress. Reprod Biol Endocrinol 2013;11:85.

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