open access

Vol 58, No 2 (2020)
ORIGINAL PAPERS
Published online: 2020-06-02
Submitted: 2020-02-24
Accepted: 2020-05-12
Get Citation

Features of gonadal dysgenesis and Leydig cell impairment in testes with Sertoli cell-only syndrome

Daria Adamczewska, Jolanta Slowikowska-Hilczer, Katarzyna Marchlewska, Renata Walczak-Jedrzejowska
DOI: 10.5603/FHC.a2020.0008
·
Pubmed: 32490535
·
Folia Histochem Cytobiol 2020;58(2):73-82.

open access

Vol 58, No 2 (2020)
ORIGINAL PAPERS
Published online: 2020-06-02
Submitted: 2020-02-24
Accepted: 2020-05-12

Abstract

Introduction. There is evidence that disturbed spermatogenesis is associated with impaired Leydig cell function and that it may be the result of testicular dysgenesis during fetal/infant development. Sertoli cell-only syndrome (SCOS) is defined by complete lack of germ cells in the seminiferous epithelium. The pathogenesis of SCOS is still not well understood. The aim of the study is to evaluate testes with SCOS focusing on morphometric signs of testicular dysgenesis and markers of Leydig cell (LC) function in relation to hormonal status of studied infertile men.

Materials and methods. Forty-nine testicular biopsies of patients with SCOS and 15 controls with normal spermatogenesis (NOR) were studied. In each biopsy the seminiferous tubule diameter (STD), thickness of tubular membrane (TM), area fraction of intertubular space (AFIS) were measured and semi-quantitative assessment of the LC number was performed (LC-score). The results of histological examination were correlated with serum levels of FSH, LH, testosterone (T) and T/LH ratio.

Results. In SCOS group testicular volume (median [M]: 16.0 vs. 29.5; p < 0.001) and STD (M: 141.7 vs. 190.2; p < 0.001) were lower, while TM (M: 9.8 vs. 6.4; p < 0.001) and AFIS (M: 47.6 vs. 27.6; p < 0.001) were significantly higher in comparison to NOR group. LC-score was higher in SCOS than in NOR group (M: 2.2 vs. 1.1;
p < 0.001). Abnormal AFIS and STD were present in 43% of SCOS biopsies and among them in 81% the increased LC-score was found. In SCOS group, the subjects had significantly higher levels of both gonadotropins (FSH, M: 19.9 vs. 3.4; p < 0.001; LH, M: 7.1 vs. 4.2; p < 0.001). Total serum testosterone level did not differ between studied groups; however, T/LH ratio was significantly lower in SCOS group (M: 2.3 vs. 3.8; p < 0.001). Negative correlation between LC-score and STD was observed in SCOS group (r = –0.48; p < 0.001). AFIS correlated positively with serum FSH level in NOR (r = 0.53; p < 0.05) and SCOS (r = 0.41; p < 0.05) group, while with LH, and negatively with T/LH ratio, only in SCOS (LH, r = 0.37; p < 0.05; T/LH, r = –0.36; p < 0.05) group.

Conclusions. We have shown that substantial number of testes from subjects with SCOS presented abnormal morphometric features, which are recognized as the signs of testicular dysgenesis. Additionally, an increased number of Leydig cells simultaneously with abnormal T/LH ratio were found, which suggests an impaired function of these cells. Increased serum levels of LH and also FSH, may reflect dysfunction of Leydig cells. It seems that reproductive hormones levels reflect also the condition of testicular structure, and that FSH may be related to the changes in intertubular space area independently of impaired Leydig cell function.

Abstract

Introduction. There is evidence that disturbed spermatogenesis is associated with impaired Leydig cell function and that it may be the result of testicular dysgenesis during fetal/infant development. Sertoli cell-only syndrome (SCOS) is defined by complete lack of germ cells in the seminiferous epithelium. The pathogenesis of SCOS is still not well understood. The aim of the study is to evaluate testes with SCOS focusing on morphometric signs of testicular dysgenesis and markers of Leydig cell (LC) function in relation to hormonal status of studied infertile men.

Materials and methods. Forty-nine testicular biopsies of patients with SCOS and 15 controls with normal spermatogenesis (NOR) were studied. In each biopsy the seminiferous tubule diameter (STD), thickness of tubular membrane (TM), area fraction of intertubular space (AFIS) were measured and semi-quantitative assessment of the LC number was performed (LC-score). The results of histological examination were correlated with serum levels of FSH, LH, testosterone (T) and T/LH ratio.

Results. In SCOS group testicular volume (median [M]: 16.0 vs. 29.5; p < 0.001) and STD (M: 141.7 vs. 190.2; p < 0.001) were lower, while TM (M: 9.8 vs. 6.4; p < 0.001) and AFIS (M: 47.6 vs. 27.6; p < 0.001) were significantly higher in comparison to NOR group. LC-score was higher in SCOS than in NOR group (M: 2.2 vs. 1.1;
p < 0.001). Abnormal AFIS and STD were present in 43% of SCOS biopsies and among them in 81% the increased LC-score was found. In SCOS group, the subjects had significantly higher levels of both gonadotropins (FSH, M: 19.9 vs. 3.4; p < 0.001; LH, M: 7.1 vs. 4.2; p < 0.001). Total serum testosterone level did not differ between studied groups; however, T/LH ratio was significantly lower in SCOS group (M: 2.3 vs. 3.8; p < 0.001). Negative correlation between LC-score and STD was observed in SCOS group (r = –0.48; p < 0.001). AFIS correlated positively with serum FSH level in NOR (r = 0.53; p < 0.05) and SCOS (r = 0.41; p < 0.05) group, while with LH, and negatively with T/LH ratio, only in SCOS (LH, r = 0.37; p < 0.05; T/LH, r = –0.36; p < 0.05) group.

Conclusions. We have shown that substantial number of testes from subjects with SCOS presented abnormal morphometric features, which are recognized as the signs of testicular dysgenesis. Additionally, an increased number of Leydig cells simultaneously with abnormal T/LH ratio were found, which suggests an impaired function of these cells. Increased serum levels of LH and also FSH, may reflect dysfunction of Leydig cells. It seems that reproductive hormones levels reflect also the condition of testicular structure, and that FSH may be related to the changes in intertubular space area independently of impaired Leydig cell function.

Get Citation

Keywords

Sertoli cell-only syndrome; testicular dysgenesis syndrome; Leydig cells; FSH; LH; testosterone; testicular biopsy; histology; morphometric assessment

About this article
Title

Features of gonadal dysgenesis and Leydig cell impairment in testes with Sertoli cell-only syndrome

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 58, No 2 (2020)

Pages

73-82

Published online

2020-06-02

DOI

10.5603/FHC.a2020.0008

Pubmed

32490535

Bibliographic record

Folia Histochem Cytobiol 2020;58(2):73-82.

Keywords

Sertoli cell-only syndrome
testicular dysgenesis syndrome
Leydig cells
FSH
LH
testosterone
testicular biopsy
histology
morphometric assessment

Authors

Daria Adamczewska
Jolanta Slowikowska-Hilczer
Katarzyna Marchlewska
Renata Walczak-Jedrzejowska

References (41)
  1. Jungwirth A, Giwercman A, Tournaye H, et al. European Association of Urology Guidelines on Male Infertility: The 2012 Update. Eur Urol. 2012; 62(2): 324–332.
  2. Krausz C. Male infertility: Pathogenesis and clinical diagnosis. Best Pract Res Clin Endocrinol Metab. 2011; 25(2): 271–285.
  3. Walczak–Jedrzejowska R, Wolski J, Slowikowska–Hilczer J. The role of oxidative stress and antioxidants in male fertility. Cent European J Urol. 2013; 65: 60–67.
  4. Gill K, Jakubik J, Kups M, et al. The impact of sedentary work on sperm nuclear DNA integrity. Folia Histochem Cytobiol. 2015.
  5. Shi H, Liu J, Zhu P, et al. Expression of peroxiredoxins in the human testis, epididymis and spermatozoa and their role in preventing H2O2-induced damage to spermatozoa. Folia Histochem Cytobiol. 2018; 56(3): 141–150.
  6. Rajert-De Me, Grigor K, Skakkebaek N. Histoathological Evaluation of Testicular Biosy. In: Lenzi A, Simoni M, Huhtaniemi I, editors. Endocrinology of the Testis and Male Reroduction. Endocrinology. Cham, Switzerland: Sringer; 2017. p. : 623–642.
  7. Lardone MC, Piottante A, Valdevenito R, et al. Histological and hormonal testicular function in oligo/azoospermic infertile men. Andrologia. 2012; 45(6): 379–385.
  8. Halder A, Jain M, Kumar P. Primary Testicular Failure: An Overview. J Clin Diag Res. 2015; 3: 1–5.
  9. Jain M, Kumar P, Iyer V, et al. Primary Testicular Failure. Basics of Human Andrology. 2017: 417–436.
  10. Cheng Y, Chung C, Chen C, et al. Differential expression of microRNAs and their messengerRNA targets in men with normal spermatogenesis versus Sertoli cell-only syndrome. Urol Sci. 2017; 28(1): 42–49.
  11. Stouffs K, Gheldof A, Tournaye H, et al. Sertoli Cell-Only Syndrome: Behind the Genetic Scenes. BioMed Res Int. 2016; 2016: 1–7.
  12. Lardone MC, Castillo P, Valdevenito R, et al. P450-aromatase activity and expression in human testicular tissues with severe spermatogenic failure. Int J Androl. 2010; 33: 650-660. .
  13. Matsumoto AM, Bremner WJ, et al. Testicular disorders. In: Melmed S, Polonsky KS, Larsen PR, , editors. Williams Textbook of Endocrinology. 13 ed: Elsevier; 2017. p. : 694–708.
  14. Andersson AM, Jørgensen N, Frydelund-Larsen L, et al. Impaired Leydig Cell Function in Infertile Men: A Study of 357 Idiopathic Infertile Men and 318 Proven Fertile Controls. J Clin Endocrinol Metab. 2004; 89(7): 3161–3167.
  15. Holm M, Meyts ERD, Andersson AM, et al. Leydig cell micronodules are a common finding in testicular biopsies from men with impaired spermatogenesis and are associated with decreased testosterone/LH ratio. J Pathol. 2003; 199(3): 378–386.
  16. Lardone MC, Argandona F, Florez M, et al. Overexpression of CYP19A1 aromatase in Leydig cells is associated with steroidogenic dysfunction in subjects with Sertoli cell-only syndrome. Andrology. 2017; 5: 41-48. .
  17. Toppari J, Skakkeb˦k N. Sexual differentiation and environmental endocrine disrupters. Baillieres Clin Endocrinol Metab. 1998; 12(1): 143–156.
  18. Sharpe R. The 'oestrogen hypothesis'- where do we stand now?1. Int J Androl. 2003; 26(1): 2–15.
  19. Guminska A, Oszukowska E, Kuzanski W, et al. Less advanced testicular dysgenesis is associated by a higher prevalence of germ cell neoplasia. Int J Androl. 2009; 33(1): e153–e162.
  20. Hoei-Hansen C, Holm M, Meyts ERD, et al. Histological evidence of testicular dysgenesis in contralateral biopsies from 218 patients with testicular germ cell cancer. J Pathol. 2003; 200(3): 370–374.
  21. Holstein AF, Roosen-Runge EC, Schirren CS. The testis biopsy. In: Holstein AF, Roosen-Runge EC, Schirren CS, editors. llustrated Pathology of Human Testes. Berlin: Grosse Verlag; 1988. p. 58–76.
  22. Weinbauer GF, Gromoll J, Simoni M, et al. Physiology of testicular function. Andrology. Male Reroductive Health and Dysfunction. Berlin, Heidelberg, New York.: Sringer Verlag; 2010. p. : 25–60.
  23. Guminska A, Slowikowska-Hilczer J, Kuzanski W, et al. Features of impaired seminiferous tubule differentiation are associated with germ cell neoplasia in adult men surgically treated in childhood because of cryptorchidism. Folia Histochem Cytobiol. 2007; 45 : S163-168, doi: https://www.ncbi.nlm.nih. gov/pubmed/18292827, indexed in Pubmed. ; 18292827.
  24. GIAGULLI VA, VERMEULEN A. Leydig Cell Function in Infertile Men with Idiopathic Oligospermic Infertility. J Clin Endocrinol Metab. 1988; 66(1): 62–67.
  25. BRUNO B, VILLA S, PROPERZI G, et al. Hormonal and Seminal Parameters in Infertile Men. Andrologia. 2009; 18(6): 595–600.
  26. Parada-Bustamante A, Molina C, Valencia C, et al. Disturbed testicular expression of the estrogen-metabolizing enzymes CYP1A1 and COMT in infertile men with primary spermatogenic failure: possible negative implications on Sertoli cells. Andrology. 2017; 5(3): 486–494.
  27. Glass AR, Vigersky RA. Leydig cell function in idiopathic oligospermia. Fertil Steril. 1980; 34: 144-148, doi: https://www.ncbi.nlm.nih. gov/pubmed/6773819, indexed in Pubmed. ; 6773819.
  28. Lardone MC, Argandoña F, Lorca M, et al. Leydig cell dysfunction is associated with post-transcriptional deregulation of CYP17A1 in men with Sertoli cell-only syndrome. MHR: Basic science of reproductive medicine. 2018; 24(4): 203–210.
  29. Fisher JS. Human 'testicular dysgenesis syndrome': a possible model using in-utero exposure of the rat to dibutyl phthalate. Hum Reprod. 2003; 18(7): 1383–1394.
  30. Foster P. Effects of phthalate esters on the developing reproductive tract of male rats. Hum Reprod Update. 2001; 7(3): 231–235.
  31. CHEMES H, MUZULIN P, VENARA M, et al. Early manifestations of testicular dysgenesis in children: pathological phenotypes, karyotype correlations and precursor stages of tumour development. APMIS. 2003; 111(1): 12–24.
  32. Cools M, Aerde Kv, Kersemaekers AM, et al. Morphological and Immunohistochemical Differences between Gonadal Maturation Delay and Early Germ Cell Neoplasia in Patients with Undervirilization Syndromes. J Clin Endocrinol Metab. 2005; 90(9): 5295–5303.
  33. Sato Y, Nozawa S, Iwamoto T. Study of spermatogenesis and thickening of lamina propria in the human seminiferous tubules. Fertil Steril. 2008; 90(4): 1310–1312.
  34. Albrecht M. Insights into the nature of human testicular peritubular cells. Ann Anat. 2009; 191(6): 532–540.
  35. Volkmann J, Muller D, Feuerstacke C, et al. Disturbed spermatogenesis associated with thickened lamina propria of seminiferous tubules is not caused by dedifferentiation of myofibroblasts. Hum Reprod. 2011; 26(6): 1450–1461.
  36. Liu Y, Zhu Y, Di L, et al. Raman spectroscopy as an ex vivo noninvasive approach to distinguish complete and incomplete spermatogenesis within human seminiferous tubules. Fertil Steril. 2014; 102(1): 54–60.e2.
  37. PANIAGUA R, MARTINEZ-ONSURBE P, SANTAMARIA L, et al. Quantitative and ultrastructural alterations in the lamina propria and Sertoli cells in human cryptorchid testes. Int J Androl. 1990; 13(6): 470–487.
  38. Martin R, Santamaría L, Nistal M, et al. The peritubular myofibroblasts in the testes from normal men and men with Klinefelter's syndrome. A quantitative, ultrastructural, and immunohistochemical study. J Pathol. 1992; 168(1): 59–66.
  39. Hadziselimovic F. Cryptorchidism. Ultrastructure of normal and cryptorchid testicular development. Berlin, Heidelberg, New York: Springer Verlag. ; 1977.
  40. Müller J, Skakkebaek N. Abnormal Germ Cells in Maldescended Testes: A Study of Cell Density, Nuclear Size and Deoxyribonucleic Acid Content in Testicular Biopsies from 50 Boys. J Urol. 1984; 131(4): 730–733.
  41. Santoro G, Romeo C, Impellizzeri P, et al. Ultrastructural and immunohistochemical study of basal lamina of the testis in adolescent varicocele. Fertil Steril. 2000; 73(4): 699–705.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl