Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The role of the prostate in male fertility, health and disease

Key Points

  • Male fertility is controlled by a Zn2+-dependent short circuit of the Krebs cycle within prostate epithelial cells

  • Homeostasis of the prostate epithelium is reliant on the intracellular androgen-dependent accumulation of Zn2+ and citrate

  • Sperm motility requires the coordinated action of the components of the two main fluids in the human seminal plasma: the prostatic fluid, which is enriched with Zn2+, citrate and kallikreins, and the semenogelin-enriched seminal vesicle secretion

  • The prostate is the direct target for a number of benign and malignant diseases that are potentially linked to impaired fertility status

  • Prostatitis might be directly linked with changes in fertility

Abstract

Ejaculation is a synchronized cascade of events that has the ultimate goal of activating sperm and enabling them to reach an egg for fertilization. The seminal plasma contains a complex mixture of fluids that is secreted from the testes, epididymis and male accessory glands. The prostate gland has a pivotal role in this process, as prostatic fluid enriched in Zn2+, citrate and kallikreins is crucial for the molecular synchronization of the functional cascade triggered by ejaculatory stimuli. The prostate is the target of a number of common diseases that can affect male fertility at different ages. In both young and aged men, prostatic diseases or an unhealthy prostate can affect spermatozoa functioning and, therefore, male fertility. Consideration of prostate physiology emphasizes a number of points: the central role of Zn2+ and citrate in the regulation of prostate epithelium homeostasis and in ejaculation; the influence of bacteria-related prostatic inflammation on male fertility; and the potential role of prostatic inflammation in promoting the development of prostatic hyperplastic growth and carcinogenesis.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Main components of the human seminal plasma (whole ejaculate) and their functional relationship.
Figure 2: Gross and microscopic anatomy of the prostate gland.

Similar content being viewed by others

References

  1. Gilany, K., Minai-Tehrani, A., Savadi-Shiraz, E., Rezadoost, H. & Lakpour, N. Exploring the human seminal plasma proteome: an unexplored gold mine of biomarker for male infertility and male reproduction disorder. J. Reprod. Infertil. 16, 61–71 (2015).

    PubMed  PubMed Central  Google Scholar 

  2. Tena-Sempere, M. Ghrelin, the gonadal axis and the onset of puberty. Endocr. Dev. 25, 69–82 (2013).

    Article  CAS  Google Scholar 

  3. Nargund, V. H. Effects of psychological stress on male fertility. Nat. Rev. Urol. 12, 373–382 (2015).

    Article  CAS  Google Scholar 

  4. Rey, R. A. et al. Male hypogonadism: an extended classification based on a developmental, endocrine physiology-based approach. Andrology 1, 3–16 (2013).

    Article  CAS  Google Scholar 

  5. Nieto, C. M., Rider, L. C. & Cramer, S. D. Influence of stromal–epithelial interactions on androgen action. Endocr. Relat. Cancer 21, T147–T160 (2014).

    Article  CAS  Google Scholar 

  6. Wagenlehner, F. et al. Prostatitis and andrological implications. Minerva Urol. Nefrol. 65, 117–123 (2013).

    CAS  PubMed  Google Scholar 

  7. Ficarra, V. et al. The role of prostatic inflammation in low urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and its potential impact on medical therapy. Curr. Urol. Rep. 15, 463–469 (2014).

    Article  Google Scholar 

  8. Wagenlehner, F. M. E. et al. The role of inflammation and infection in the pathogenesis of prostate carcinoma. BJU Int. 100, 733–737 (2007).

    Article  CAS  Google Scholar 

  9. Roberts, R. O., Lieber, M. M., Bostwick, D. G. & Jacobsen, S. J. A review of clinical and pathological prostatitis syndromes. Urology 49, 809–821 (1997).

    Article  CAS  Google Scholar 

  10. Kalinska, M., Meyer-Hoffert, U., Kantyka, T., Potempa, J. Kallikreins. The melting pot of activity and function. Biochimie 122, 270–282 (2016).

    Article  CAS  Google Scholar 

  11. Medrano, A. et al. Utilization of citrate and lactate through a lactate dehydrogenase and ATP-regulated pathway in boar spermatozoa. Mol. Reprod. Dev. 73, 369–378 (2006).

    Article  CAS  Google Scholar 

  12. Franz, M. C. et al. Zinc transporters in prostate cancer. Mol. Aspects Med. 34, 735–741 (2013).

    Article  CAS  Google Scholar 

  13. Franklin, R. B., Milon, B., Feng, P. & Costello, L. C. Zinc and zinc transporters in normal prostate and the pathogenesis of prostate cancer. Front. Biosci. 10, 2230–2239 (2005).

    Article  CAS  Google Scholar 

  14. Lorenzetti, S. & Narciso, L. in Computational Approaches To Nuclear Receptors (eds Cozzini, P. & Kellogg, G. E.) 1–22 (RSC Publishing, 2012).

    Book  Google Scholar 

  15. Takayama, K. & Inoue, S. Transcriptional network of androgen receptor in prostate cancer progression. Int. J. Urol. 20, 756–768 (2013).

    Article  CAS  Google Scholar 

  16. Horie-Inoue, K. & Inoue, S. Genome-wide integrated analyses of androgen receptor signaling in prostate cancer based on high-throughput technology. Curr. Drug Targets 14, 472–480 (2013).

    Article  CAS  Google Scholar 

  17. Lamont, K. R. & Tindall, D. J. Androgen regulation of gene expression. Adv. Cancer Res. 107, 137–162 (2010).

    Article  CAS  Google Scholar 

  18. Johnson, L. A., Kanak, M. A., Kajdacsy-Balla, A., Pestaner, J. P. & Bagasra, O. Differential zinc accumulation and expression of human zinc transporter 1 (hZIP1) in prostate glands. Methods 52, 316–321 (2010).

    Article  CAS  Google Scholar 

  19. Costello, L. C. & Franklin, R. B. The clinical relevance of the metabolism of prostate cancer; zinc and tumor suppression: connecting the dots. Mol. Cancer 5, 17 (2006).

    Article  Google Scholar 

  20. Franklin, R. B. et al. hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer. Mol. Cancer 4, 32 (2005).

    Article  Google Scholar 

  21. Desouki, M. M., Geradts, J., Milon, B., Franklin, R. B. & Costello, L. C. hZip2 and hZip3 zinc transporters are down regulated in human prostate adenocarcinomatous glands. Mol. Cancer 6, 37 (2007).

    Article  Google Scholar 

  22. Kolenko, V., Teper, E., Kutikov, A. & Uzzo, R. Zinc and zinc transporters in prostate carcinogenesis. Nat. Rev. Urol. 10, 219–226 (2013).

    Article  CAS  Google Scholar 

  23. Tepaamorndech, S., Huang, L. & Kirschke, C. P. A null-mutation in the Znt7 gene accelerates prostate tumor formation in a transgenic adenocarcinoma mouse prostate model. Cancer Lett. 308, 33–42 (2011).

    Article  CAS  Google Scholar 

  24. Thorek, D. L., Evans, M. J., Carlsson, S. V., Ulmert, D. & Lilja, H. Prostate-specific kallikrein-related peptidases and their relation to prostate cancer biology and detection. Thromb. Haemost. 110, 484–492 (2013).

    Article  CAS  Google Scholar 

  25. Bartoletti, R. et al. Prevalence, incidence estimation, risk factors and characterization of chronic prostatitis/chronic pelvic pain syndrome in urological hospital outpatients in Italy: results of a multicenter case-control observational study. J. Urol. 178, 2411–2415 (2007).

    Article  Google Scholar 

  26. Domes, T. et al. The incidence and effect of bacteriospermia and elevated seminal leukocytes on semen parameters. Fertil. Steril. 97, 1050–1055 (2012).

    Article  Google Scholar 

  27. Mändar, R., Raukas, E., Tu¨rk, S., Korrovits, P. & Punab, M. Mycoplasmas in semen of chronic prostatitis patients. Scand. J. Urol. Nephrol. 39, 479–482 (2005).

    Article  Google Scholar 

  28. Fraczek, M. et al. Membrane stability and mitochondrial activity of human-ejaculated spermatozoa during in vitro experimental infection with Escherichia coli, Staphylococcus haemolyticus and Bacteroides ureolyticus. Andrologia 44, 315–329 (2012).

    Article  CAS  Google Scholar 

  29. Schulz, M., Sánchez, R., Soto, L., Risopatrón, J. & Villegas, J. Effect of Escherichia coli and its soluble factors on mitochondrial membrane potential, phosphatidylserine translocation, viability, and motility of human spermatozoa. Fertil. Steril. 94, 619–623 (2010).

    Article  CAS  Google Scholar 

  30. Diemer, T. et al. Escherichia coli-induced alterations of human spermatozoa. An electron microscopy analysis. Int. J. Androl. 23, 178–186 (2000).

    Article  CAS  Google Scholar 

  31. Marconi, M., Pilatz, A., Wagenlehner, F., Diemer, T. & Weidner, W. Impact of infection on the secretory capacity of the male accessory glands. Int. Braz. J. Urol. 35, 299–309 (2000).

    Article  Google Scholar 

  32. Dobrindt, U., Hochhut, B., Hentschel, U. & Hacker, J. Genomic islands in pathogenic and environmental microorganisms. Nat. Rev. Microbiol. 2, 414–424 (2004).

    Article  CAS  Google Scholar 

  33. Marrs, C. F., Zhang, L. & Foxman, B. Escherichia coli mediated urinary tract infections: are there distinct uropathogenic E. coli (UPEC) pathotypes? FEMS Microbiol. Lett. 252, 183–190 (2005).

    Article  CAS  Google Scholar 

  34. Dhakal, B. K. & Mulvey, M. A. The UPEC pore-forming toxin α-hemolysin triggers proteolysis of host proteins to disrupt cell adhesion, inflammatory, and survival pathways. Cell Host Microbe 11, 58–69 (2012).

    Article  CAS  Google Scholar 

  35. Diemer, T., Ludwig, M., Huwe, P., Hales, B. & Weidner, W. Influence of urogenital infection on sperm function. Curr. Opin. Urol. 10, 39–44 (2000).

    Article  CAS  Google Scholar 

  36. Kaur, K. & Prabha, V. Impairment by sperm agglutinating factor isolated from Escherichia coli: receptor specific interactions. Biomed. Res. Int. 54, 84–97 (2013).

    Google Scholar 

  37. Ludwig, M. et al. Experimental Escherichia coli epididymitis in rats: a model to assess the outcome of antibiotic treatment. BJU Int. 90, 933–938 (2002).

    Article  CAS  Google Scholar 

  38. Lu, Y. et al. Necrosis is the dominant cell death pathway in uropathogenic Escherichia coli elicited epididymo-orchitis and is responsible for damage of rat testis. PLoS ONE 8, e52919 (2013).

    Article  CAS  Google Scholar 

  39. Bhushan, S. et al. Uropathogenic Escherichia coli block MyD88-dependent and activate MyD88-independent signaling pathways in rat testicular cells. J. Immunol. 180, 5537–5547 (2008).

    Article  CAS  Google Scholar 

  40. Dohle, G. R. Inflammatory-associated obstructions of the male reproductive tract. Andrologia 35, 321–324 (2003).

    Article  CAS  Google Scholar 

  41. Cai, T., Mazzoli, S., Mondaini, N., Malossini, G. & Bartoletti, R. Chlamydia trachomatis infection: a challenge for the urologist. Microbiol. Res. 2, e14 (2011).

    Article  Google Scholar 

  42. Krishnan, R. & Heal, M. R. Study of the seminal vesicles in acute epididymitis. Br. J. Urol. 67, 632–637 (1991).

    Article  CAS  Google Scholar 

  43. Alwaal, A., Breyer, B. N. & Lue, T. F. Normal male sexual function: emphasis on orgasm and ejaculation. Fertil. Steril. 104, 1051–1060 (2015).

    Article  Google Scholar 

  44. Eley, A., Pacey, A. A., Galdiero, M., Galdiero, M. & Galdiero, F. Can Chlamydia trachomatis directly damage your sperm? Lancet Infect. Dis. 5, 53–57 (2005).

    Article  Google Scholar 

  45. Erbengi, T. Ultrastructural observations on the entry of Chlamydia trachomatis into human spermatozoa. Hum. Reprod. 8, 416–421 (1993).

    Article  CAS  Google Scholar 

  46. Munoz, G., Posnett, D. N. & Witkin, S. S. Enrichment of γδ T lymphocytes in human semen: relation between γδ T cell concentration and antisperm antibody status. J. Reprod. Immunol. 22, 47–57 (1992).

    Article  CAS  Google Scholar 

  47. Karinen, L. et al. Antibodies to Chlamydia trachomatis heat shock proteins Hsp60 and Hsp10 and subfertility in general population at age 31. Am. J. Reprod. Immunol. 52, 291–297 (2004).

    Article  CAS  Google Scholar 

  48. Domeika, M., Domeika, K., Paavonen, J., Mardh, P. A. & Witkin, S. S. Humoral immune response to conserved epitopes of Chlamydia trachomatis and human 60-kDa heat-shock protein in women with pelvic inflammatory disease. J. Infect. Dis. 177, 714–719 (1998).

    Article  CAS  Google Scholar 

  49. Mazzoli, S. Chlamydia trachomatis infection is related to poor semen quality in young prostatitis patients. Eur. Urol. 57, 708–714 (2010).

    Article  Google Scholar 

  50. Leib, Z., Bartoov, B., Eltes, F. & Servadio, C. Reduced semen quality caused by chronic abacterial prostatitis: an enigma or reality? Fertil. Steril. 61, 1109–1116 (1994).

    Article  CAS  Google Scholar 

  51. Potts, J. M. & Pasqualotto, F. F. Seminal oxidative stress in patients with chronic prostatitis. Andrologia 35, 304–308 (2003).

    Article  CAS  Google Scholar 

  52. Showell, M. G. et al. Antioxidants for male subfertility. Cochrane Database Syst. Rev. 12, CD007411 (2014).

    Google Scholar 

  53. Hochreiter, W. W., Duncan, J. L. & Schaeffer, A. J. Evaluation of the bacterial flora of the prostate using a 16S rRNA gene based polymerase chain reaction. J. Urol. 163, 127–130 (2000).

    Article  CAS  Google Scholar 

  54. Kaur, K. & Prabha, V. Spermagglutinating Escherichia coli and its role in infertility: in vivo study. Microb. Pathog. 69–70, 33–38 (2014).

  55. Ochsendorf, F. R. et al. Chlamydia trachomatis and male infertility: Chlamydia-IgA antibodies in seminal plasma are C. trachomatis specific and associated with an inflammatory response. J. Eur. Acad. Dermatol. Venereol. 12, 143–152 (1999).

    Article  CAS  Google Scholar 

  56. Cai, T. et al. Semen quality in patients with Chlamydia trachomatis genital infection treated concurrently with prulifloxacin and a phytotherapeutic agent. J. Androl. 33, 615–623 (2012).

    Article  CAS  Google Scholar 

  57. Steiner, G. et al. Phenotype and function of peripheral and prostatic lymphocytes in patients with benign prostatic hyperplasia. J. Urol. 151, 480–484 (1994).

    Article  CAS  Google Scholar 

  58. Gandaglia, G. et al. The role of chronic prostatic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH). BJU Int. 112, 432–441 (2013).

    Article  Google Scholar 

  59. Shah, R., Mucci, N. R., Amin, A., Macoska, J. A. & Rubin, M. A. Postatrophic hyperplasia of the prostate gland: neoplastic precursor or innocent bystander? Am. J. Pathol. 158, 1767–1773 (2001).

    Article  CAS  Google Scholar 

  60. Elkahwaji, J. E., Zhong, W., Hopkins, W. J. & Bushman, W. Chronic bacterial infection and inflammation incite reactive hyperplasia in a mouse model of chronic prostatitis. Prostate 67, 14–21 (2007).

    Article  Google Scholar 

  61. Simons, B. W. et al. A human prostatic bacterial isolate alters the prostatic microenvironment and accelerates prostate cancer progression. J. Pathol. 235, 478–489 (2015).

    Article  CAS  Google Scholar 

  62. Sampson, N. et al. The ageing male reproductive tract. J. Pathol. 211, 206–218 (2007).

    Article  CAS  Google Scholar 

  63. Untergasser, G. et al. Proliferative disorders of the aging human prostate: involvement of protein hormones and their receptors. Exp. Gerontol. 34, 275–287 (1999).

    Article  CAS  Google Scholar 

  64. Hoover, P. & Naz, R. K. Do men with prostate abnormalities (prostatitis/benign prostatic hyperplasia/prostate cancer) develop immunity to spermatozoa or seminal plasma? Int. J. Androl. 35, 608–615 (2012).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

P.V., T.C. and S.L. equally contributed to researching data for the article, discussion of content, writing and reviewing/editing of the manuscript under the coordination of the corresponding author.

Corresponding author

Correspondence to Paolo Verze.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Verze, P., Cai, T. & Lorenzetti, S. The role of the prostate in male fertility, health and disease. Nat Rev Urol 13, 379–386 (2016). https://doi.org/10.1038/nrurol.2016.89

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrurol.2016.89

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing