International Urology and Nephrology

, Volume 46, Issue 5, pp 879–885 | Cite as

Quantitative histological analysis and ultrastructure of the aging human testis

Urology - Original Paper



To quantitatively assess the histological and ultrastructural changes resulting from aging in the human testis.


Age-related histological and ultrastructural changes were evaluated using light microscopy, transmission electron microscopy (TEM) and immunohistochemistry on 41 testicular samples obtained from elderly men and, respectively, assigned to group A (n = 20), 54–69 years old or group B (n = 21), 70–89 years old. Testicular samples derived from 17 young men were used for control.


The numbers of Sertoli cells in the aged groups were significantly lower than that in the controls (p < 0.05). With the exception of the Sertoli cell ratios (germ cells/Sertoli cells) of spermatogonia and primary spermatocytes, results showed lower levels of the Sertoli cell ratios of round spermatids and elongated spermatids in the elderly men compared with the young men (p < 0.05). A similar degenerative pattern of the organelles was shown in germ cells and Sertoli cells in the aging testes under TEM. Immunohistochemistry revealed an increased apoptosis index (AI) (0.81 ± 0.13) accompanied by a decreased proliferation index (PI) (30.08 ± 4.86) in the group B (p < 0.05), while both AI and PI were similar between the group A (0.54 ± 0.06; 36.38 ± 7.38) and the controls (0.50 ± 0.15; 40.55 ± 7.92) (p > 0.05).


Aging has negative influence on testicular morphology and spermatogenesis, and the failure of spermatogenic cell development is evident from the spermatid level.


Aging Testis Spermatogenesis Apoptosis Proliferation 



This work was financed by the National “Twelfth Five-Year” Plan for Science and Technology Support (2012BAI32B03).

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Eskenazi B, Wyrobek AJ, Sloter E, Kidd SA, Moore L, Young S, Moore D (2003) The association of age and semen quality in healthy men. Hum Reprod 18:447–454PubMedCrossRefGoogle Scholar
  2. 2.
    Haidl G, Jung A, Schill WB (1996) Ageing and sperm function. Hum Reprod 11:558–560PubMedCrossRefGoogle Scholar
  3. 3.
    Plas E, Berger P, Hermann M, Pfluger H (2000) Effects of aging on male fertility? Exp Gerontol 35:543–551PubMedCrossRefGoogle Scholar
  4. 4.
    Pop OT, Cotoi CG, Plesea IE, Enache SD, Popescu FC, Enache MA, Plesea RM (2011) Correlations between intralobular interstitial morphological changes and epithelial changes in ageing testis. Rom J Morphol Embryol 52:339–347PubMedGoogle Scholar
  5. 5.
    Neaves WB, Johnson L, Porter JC, Parker CR Jr, Petty CS (1984) Leydig cell numbers, daily sperm production, and serum gonadotropin levels in aging men. J Clin Endocrinol Metab 59:756–763PubMedCrossRefGoogle Scholar
  6. 6.
    Paniagua R, Martin A, Nistal M, Amat P (1987) Testicular involution in elderly men: comparison of histologic quantitative studies with hormone patterns. Fertil Steril 47:671–679PubMedGoogle Scholar
  7. 7.
    Well D, Yang H, Houseni M, Iruvuri S, Alzeair S, Sansovini M, Wintering N, Alavi A, Torigian DA (2007) Age-related structural and metabolic changes in the pelvic reproductive end organs. Semin Nucl Med 37:173–184PubMedCrossRefGoogle Scholar
  8. 8.
    Xia Y, Zhu WJ, Hao SF, Liang WB, Li J (2012) Stereological analysis of age-related changes of testicular peritubular cells in men. Arch Gerontol Geriatr 55:116–119PubMedCrossRefGoogle Scholar
  9. 9.
    Chen QJ, Zhu WJ, Li J (2006) Effects of aging on spermatogenesis, sperm maturation and fertility in mice. J Reprod Contracept 17:9–14Google Scholar
  10. 10.
    Hellstrom WJ, Overstreet JW, Sikka SC, Denne J, Ahuja S, Hoover AM, Sides GD, Cordell WH, Harrison LM, Whitaker JS (2006) Semen and sperm reference ranges for men 45 years of age and older. J Androl 27:421–428PubMedCrossRefGoogle Scholar
  11. 11.
    Russell LD, Malone JP, Karpas SL (1981) Morphological pattern elicited by agents affecting spermatogenesis by stimulation. Tissue Cell 13:369–380PubMedCrossRefGoogle Scholar
  12. 12.
    Paniagua R, Nistal M, Saez FJ, Fraile B (1991) Ultrastructure of the aging human testis. J Electron Microsc Tech 19:241–260PubMedCrossRefGoogle Scholar
  13. 13.
    Paniagua R, Nistal M, Amat P, Rodriguez MC, Martin A (1987) Seminiferous tubule involution in elderly men. Biol Reprod 36:939–947PubMedCrossRefGoogle Scholar
  14. 14.
    Hikim AP, Wang C, Lue Y, Johnson L, Wang XH, Swerdloff RS (1998) Spontaneous germ cell apoptosis in humans: evidence for ethnic differences in the susceptibility of germ cells to programmed cell death. J Clin Endocrinol Metab 83:152–156PubMedCrossRefGoogle Scholar
  15. 15.
    Kimura M, Itoh N, Takagi S, Sasao T, Takahashi A, Masumori N, Tsukamoto T (2003) Balance of apoptosis and proliferation of germ cells related to spermatogenesis in aged men. J Androl 24:185–191PubMedGoogle Scholar
  16. 16.
    Levy S, Serre V, Hermo L, Robaire B (1999) The effects of aging on the seminiferous epithelium and the blood-testis barrier of the Brown Norway rat. J Androl 20:356–365PubMedGoogle Scholar
  17. 17.
    Yan HH, Cheng CY (2005) Blood-testis barrier dynamics are regulated by an engagement/disengagement mechanism between tight and adherens junctions via peripheral adaptors. Proc Natl Acad Sci USA 102:11722–11727PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Lui WY, Lee WM (2009) Molecular mechanisms by which hormones and cytokines regulate cell junction dynamics in the testis. J Mol Endocrinol 43:43–51PubMedCrossRefGoogle Scholar
  19. 19.
    Perheentupa A, Huhtaniemi I (2009) Aging of the human ovary and testis. Mol Cell Endocrinol 299:2–13PubMedCrossRefGoogle Scholar
  20. 20.
    Pastor LM, Zuasti A, Ferrer C, Bernal-Manas CM, Morales E, Beltran-Frutos E, Seco-Rovira V (2011) Proliferation and apoptosis in aged and photoregressed mammalian seminiferous epithelium, with particular attention to rodents and humans. Reprod Domest Anim 46:155–164PubMedCrossRefGoogle Scholar
  21. 21.
    Salama M, Tsuji M, Tamura M, Kagawa S (1998) Impact of aging and diabetes mellitus on the expression of the proliferating cell nuclear antigen in rat testicular tissue. Arch Androl 40:95–107PubMedCrossRefGoogle Scholar
  22. 22.
    Johnson L, Nguyen HB, Petty CS, Neaves WB (1987) Quantification of human spermatogenesis: germ cell degeneration during spermatocytogenesis and meiosis in testes from younger and older adult men. Biol Reprod 37:739–747PubMedCrossRefGoogle Scholar
  23. 23.
    Johnson L, Grumbles JS, Bagheri A, Petty CS (1990) Increased germ cell degeneration during postprophase of meiosis is related to increased serum follicle-stimulating hormone concentrations and reduced daily sperm production in aged men. Biol Reprod 42:281–287PubMedCrossRefGoogle Scholar
  24. 24.
    Johnson L, Petty CS, Neaves WB (1983) Further quantification of human spermatogenesis: germ cell loss during postprophase of meiosis and its relationship to daily sperm production. Biol Reprod 29:207–215PubMedCrossRefGoogle Scholar
  25. 25.
    Syed V, Hecht NB (2002) Disruption of germ cell-Sertoli cell interactions leads to spermatogenic defects. Mol Cell Endocrinol 186:155–157PubMedCrossRefGoogle Scholar
  26. 26.
    Syed V, Hecht NB (2001) Selective loss of Sertoli cell and germ cell function leads to a disruption in sertoli cell-germ cell communication during aging in the Brown Norway rat. Biol Reprod 64:107–112PubMedCrossRefGoogle Scholar
  27. 27.
    Murray MJ, Meacham RB (1993) The effect of age on male reproductive function. World J Urol 11:137–140PubMedCrossRefGoogle Scholar
  28. 28.
    Skinner MK, Tung PS, Fritz IB (1985) Cooperativity between Sertoli cells and testicular peritubular cells in the production and deposition of extracellular matrix components. J Cell Biol 100:1941–1947PubMedCrossRefGoogle Scholar
  29. 29.
    Richardson LL, Kleinman HK, Dym M (1995) Basement membrane gene expression by Sertoli and peritubular myoid cells in vitro in the rat. Biol Reprod 52:320–330PubMedCrossRefGoogle Scholar
  30. 30.
    Richardson LL, Kleinman HK, Dym M (1995) The effects of aging on basement membrane in the testis. J Androl 16:118–126PubMedGoogle Scholar
  31. 31.
    Kondarewicz A, Kolasa A, Zawislak B, Baranowska-Bosiacka I, Marchlewicz M, Wenda-Rozewicka L, Wiszniewska B (2011) Testis morphology in rats chronically treated with letrozole, an aromatase inhibitor. Folia Histochem Cytobiol 49:677–684PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Institute of Reproductive Immunology, College of Life Science and TechnologyJinan UniversityGuangzhouPeople’s Republic of China
  2. 2.Department of Pathophysiology, Medical CollegeJinan UniversityGuangzhouPeople’s Republic of China
  3. 3.Department of Urology, The First Affiliated HospitalJinan UniversityGuangzhouPeople’s Republic of China
  4. 4.National Research Institute for Family PlanningBeijingPeople’s Republic of China

Personalised recommendations