Skip to main content
Log in

Sertoli cell-only syndrome: etiology and clinical management

  • Review
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Almost 50% of infertility cases are due to male factors, and spermatogenesis failure is one of the most severe forms of male infertility. Sertoli cell-only syndrome (SCOS) also known as germ cell aplasia is characterized by azoospermia in which the seminiferous tubules of testicular biopsy are lined only with Sertoli cells. The definitive diagnosis of SCOS is by diagnostic testicular biopsy. Although SCOS may be a result of Klinefelter syndrome, most of the SCOS men have a normal karyotype. Along with genetic aberrations, signaling pathways and endocrine processes might be major factors in the development of SCOS. Sperm retrieval and intracytoplasmic sperm injection (ICSI) are available treatments for SCOS. However, some SCOS patients do not have therapeutic options to help them having a biological child. This review aims to summarize our present knowledge about SCOS and to highlight the importance of future researches in the diagnosis and treatment of this disorder.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Eisenberg ML, Lathi RB, Baker VL, Westphal LM, Milki AA, Nangia AK. Frequency of the male infertility evaluation: data from the national survey of family growth. J Urol [Internet]. Elsevier Inc. 2013;189:1030–4. https://doi.org/10.1016/j.juro.2012.08.239.

    Article  Google Scholar 

  2. Pan MM, Hockenberry MS, Kirby EW, Lipshultz LI. Male infertility diagnosis and treatment in the era of in vitro fertilization and intracytoplasmic sperm injection. Med Clin NA [Internet]. 2017;10:1–7. https://doi.org/10.1016/j.mcna.2017.10.008.

    Article  Google Scholar 

  3. Tournaye H, Krausz C, Oates RD. Male reproductive impairment 2 Concepts in diagnosis and therapy for male reproductive impairment. LANCET Diabetes Endocrinol [Internet]. 2016;8587:1–11. https://doi.org/10.1016/S2213-8587(16)30043-2.

    Article  Google Scholar 

  4. McLachlan RI, Rajpert-De Meyts E, Hoei-Hansen CE, de Kretser DM, Skakkebaek NE. Histological evaluation of the human testis - approaches to optimizing the clinical value of the assessment: Mini Review. Hum Reprod. 2007;22:2–16.

    Article  PubMed  CAS  Google Scholar 

  5. Ammal PL, Das SK. Testicular biopsy in male infertility. J Med Sci Clin Res. 2017;05:20616–9.

    Article  Google Scholar 

  6. Franco G, Scarselli F, Casciani V, De Nunzio C, Dente D, Leonardo C, et al. A novel stepwise micro-TESE approach in non obstructive azoospermia. BMC Urol. 2016;16:20.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Koc G, Ozdemir AA, Girgin G, Akbal C, Kirac D, Avcilar T, et al. Male infertility in Sertoli cell-only syndrome: An investigation of autosomal gene defects. Int J Urol. 2019;26:292–8.

    Article  PubMed  CAS  Google Scholar 

  8. Del Castillo EB, Trabucco A, DE la Balze FA. Syndrome produced by absence of the germinal epithelium without impairment of the Sertoli or Leydig cells. J Clin Endocrinol Metab. 1947;7:493–502.

    Article  Google Scholar 

  9. Silber SJ. Microsurgical TESE and the distribution of spermatogenesis in non-obstructive azoospermia. Hum Reprod. 2000;15:2278–84.

    Article  PubMed  CAS  Google Scholar 

  10. Anniballo R, Ubaldi F, Cobellis L, Sorrentino M, Rienzi L, Greco E, et al. Criteria predicting the absence of spermatozoa in the Sertoli cell-only syndrome can be used to improve success rates of sperm retrieval. 2000;15:2269–77.

  11. Terada T, Hatakeyama S. Morphological evidence for two types of idiopathic ‘ Sertoli-cell-only ’ syndrome. Int J Androl. 1991;14:117–26.

    Article  PubMed  CAS  Google Scholar 

  12. Nistal M, Jimenez F, Paniagua R. Sertoli cell types in the Sertoli-cell-only syndrome: relationships between Sertoli cell morphology and aetiology. Histopathology. 1990;16:173–80.

    Article  PubMed  CAS  Google Scholar 

  13. Weller O, Yogev L, Yavetz H, Paz G, Kleiman S, Hauser R. Differentiating between primary and secondary Sertoli-cell-only syndrome by histologic and hormonal parameters. Fertil Steril. 2005;83:1856–8.

    Article  PubMed  Google Scholar 

  14. Franke FE, Pauls K, Rey R, Marks A, Bergmann M, Steger K. Differentiation markers of Sertoli cells and germ cells in fetal and early postnatal human testis. Anat Embryol (Berl). 2004;209:169–77.

    PubMed  CAS  Google Scholar 

  15. Brehm R, Steger K. Regulation of Sertoli cell and germ cell differentation. Adv Anat Embryol Cell Biol [Internet]. 2005;181:1–93 Available from: http://europepmc.org/abstract/MED/16281455.

    CAS  Google Scholar 

  16. Ooba T, Ishikawa T, Yamaguchi K, Kondo Y. Expression and distribution of laminin chains in the testis for patients with azoospermia. J Androl. 2008;29:147–52.

    Article  PubMed  CAS  Google Scholar 

  17. Bibro MC, Fourcroy JL, Charles EM. A unique case of Sertoli cell only syndrome with normal gonadotropins * t. Fertil Steril [Internet]. Elsevier Masson SAS. 1984;42:655–8. https://doi.org/10.1016/S0015-0282(16)48156-2.

    Article  CAS  Google Scholar 

  18. Abdalla MI, Ibrahim II, Rizk AM, Agouz WTEL, Girgis SM. Endocrine studies of azoospermia. 1. Serum steroid levels in Sertoli cell only syndrome. Arch Androl. 1979;256:253–6.

    Article  Google Scholar 

  19. Heath H. Plasma gonadotropins in germinal cell aplasia ( Sertoli cell only syndrome). J Urol [Internet]. The American Urological Association Education and Research, Inc. 1973;109:847–9. https://doi.org/10.1016/S0022-5347(17)60560-3.

    Article  Google Scholar 

  20. Pineau C, Sharpe RM, Saunders PT, Gérard N, Jégou B. Regulation of Sertoli cell inhibin production and of inhibin alpha-subunit mRNA levels by specific germ cell types. Mol Cell Endocrinol. Ireland. 1990;72:13–22.

    Article  CAS  Google Scholar 

  21. Zarate A, Garrido J, Canales ES, Soria J, Schally AV. Disparity in the negative gonadal feedback control for LH and FSH secretion in cases of germinal aplasia or Sertoli-cell-only syndrome. JCE M. 1974:1973–5.

  22. Ishida H, Isurugi K, Aso Y, Takayasu H, Tamaoki B-I. Endocrine studies in Sertoli-cell-only syndrome. J Urol [Internet]. The American Urological Association Education and Research, Inc.; 1976;116:56–58. Available from: https://doi.org/10.1016/S0022-5347(17)58673-5

  23. Micic S, Ilic V, Micic M, Cenbacev O, Dotlic R. Endocrine Profile of 45 Patients with Sertoli cell only syndrome. Andrologia. 1983;15:228–32.

    Article  PubMed  CAS  Google Scholar 

  24. Kostakopoulos A, Protoyerou V, Tekerlekis P, Georgoulakis J, Louras G, Goulandris N. DNA flow-cytometric, histological and hormonal analysis of sertoli cell only syndrome (SECOS). Int Urol Nephrol. 2002;33:77–9.

    Article  PubMed  CAS  Google Scholar 

  25. Leifke E, Simoni M, Kamischke A, Gromoll J, Bergmann M, Nieschlag E. Does the gonadotrophic axis play a role in the pathogenesis of Sertoli-cell-only syndrome ? Int J Androl. 1997;36:29–36.

    Article  Google Scholar 

  26. Okuyama A, Nonomura N, Koh E, Kondoh N, Nakamura M, Namiki M, et al. Testicular FSH and hCG receptors in sertoli cell only syndrome. Arch Androl. 1989;124:119–24.

    Article  Google Scholar 

  27. Loukil LH, Boudawara TS, Ayadi I, Bahloul A, Jlidi R, And HA, et al. High androgen receptor immunoexpression in Human " Sertoli cell only " testis. Arcbs Inst Pasteur Tunis. 2005;82:1–4.

    Google Scholar 

  28. Han Y, Feng HL, Ssandlow JI, Haines CJ. Comparing expression of progesterone and estrogen receptors in testicular tissue from men with obstructive and nonobstructive azoospermia. J Androl. 2009;30:127–33.

    Article  PubMed  Google Scholar 

  29. Hammar M, Berg AA. Impaired leydig cell function in vitro in testicular tissue from human males with “Sertoli Cell Only” syndrome. Andrologia. 1985;17:37–41.

    Article  PubMed  CAS  Google Scholar 

  30. Lardone MC, Castillo P, Valdevenito R, Ebensperger M, Ronco AM, Pommer R. P450-aromatase activity and expression in human testicular tissues with severe spermatogenic failure. Int J Androl. 2009;33:650–60.

    PubMed  Google Scholar 

  31. Lardone MC, Argando F, Florez M, Parada-Bustamante A, Ebensperger M, Palma C, et al. Overexpression of CYP19A1 aromatase in Leydig cells is associated with steroidogenic dysfunction in subjects with Sertoli cell-only syndrome. Andrology. 2016:1–8.

  32. Malabu UH, Gowda D, Tan YM. Case report insulinoma presenting with long-standing depression , primary hypogonadism , and Sertoli cell only syndrome. Case Rep Endocrinol. 2013;2013:12–4.

    Google Scholar 

  33. Stouffs K, Gheldof A, Tournaye H, Vandermaelen D, Bonduelle M, Lissens W, et al. Sertoli Cell-only syndrome : behind the genetic scenes. Biomed Res Int. 2016;2016:6191307.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Paulis G. Chromosomic causes of infertility. Clin Manag Male Infertil. 8th ed. 2014:63–77.

  35. De Kretser DM. Male infertility genetics - The future. J Androl. 2001;22:738–46.

    PubMed  Google Scholar 

  36. Jain M, Chaudhary I, Halder A. The Sertoli cell only syndrome and glaucoma in a sex – determining region Y ( SRY ) positive XX infertile male. J Clin Diagnostic Res. 2013;7:1457–9.

    Google Scholar 

  37. Lin YH, Chuang L, Lin YM, Lin YH, Teng YN, Kuo PL. Isochromosome of Yp in a man with Sertoli-cell-only syndrome. Fertil Steril. 2005;83:764–6.

    Article  PubMed  CAS  Google Scholar 

  38. Singh V, Bala R, Chakraborty A, Rajender S, Trivedi S, Singh K. Duplications in 19p13.3 are associated with male infertility. J Assist Reprod Genet. Journal of Assisted Reproduction and Genetics. 2019;36:2171–9.

    Article  PubMed  Google Scholar 

  39. Ghorbel M, Baklouti-gargouri S, Elghazel H, Zribi N, Ben F, Cherif M, et al. Biochemical and Biophysical Research Communications Pericentric inversion of chromosom 12 [ Inv ( 12 ) ( p12q12 )] associated with idiopathic azoospermia in one infertile Tunisian man. Biochem Biophys Res Commun [Internet]. 2013;432:472–4. https://doi.org/10.1016/j.bbrc.2013.01.110.

    Article  CAS  Google Scholar 

  40. De Rosa M, De Brasi D, Zarrilli S, Paesano L, Agostino RPAD, Longobardi S, et al. Short stature and azoospermia in a patient with Y chromosome long arm deletion. J Endocrinol Invest. 1997;20:623–8.

    Article  PubMed  Google Scholar 

  41. Ichioka K, Yoshimura K, Honda T, Takahashi A. Paracentric inversion of chromosome 7 ( q22 – 31 ) associated with nonobstructive azoospermia. Fertil Steril. 2005;83:2004–5.

    Article  Google Scholar 

  42. Kamp C, Huellen K, Fernandes S, Sousa M, Schlegel PN, Mielnik A, et al. High deletion frequency of the complete AZFa sequence in men with Sertoli-cell-only syndrome. Mol Hum Reprod. 2001;7:987–94.

    Article  PubMed  CAS  Google Scholar 

  43. Ferras C, Fernandes S, Marques CJ, Carvalho F, Alves C, Silva J, et al. AZF and DAZ gene copy-specific deletion analysis in maturation arrest and Sertoli cell-only syndrome. Mol Hum Reprod. 2004;10:755–61.

    Article  PubMed  CAS  Google Scholar 

  44. Steirteghem V, Stouffs K, Lissens W, Tournaye H, Liebaers I. Possible role of USP26 in patients with severely impaired spermatogenesis. Eur J Hum Genet. 2005;26:336–40.

    Google Scholar 

  45. Gerber J, Heinrich J, Brehm R. Blood-testis barrier and Sertoli cell function: Lessons from SCCx43KO mice. Reproduction. 2016;151:R15–27.

    Article  PubMed  CAS  Google Scholar 

  46. Miyamoto T, Bando Y, Koh E, Tsujimura A, Miyagawa Y, Iijima M, et al. A PLK4 mutation causing azoospermia in a man with Sertoli cell-only syndrome. Andrology. 2016;4:75–81.

    Article  PubMed  CAS  Google Scholar 

  47. Defamie N, Berthaut I, Mograbi B, Chevallier D, Dadoune JP, Fénichel P, et al. Impaired gap junction connexin43 in Sertoli cells of patients with secretory azoospermia: a marker of undifferentiated Sertoli cells. Lab Investig. 2003;83:449–56.

    Article  PubMed  CAS  Google Scholar 

  48. Yatsenko AN. ETV5 mutations: revisiting Sertoli cell only syndrome. Fertil Steril. 2012;98:5–6.

    Article  Google Scholar 

  49. Maduro MR, Niederberger C, Lipshultz LI, Casella R, Kim E, Le N, et al. Microsatellite instability and defects in mismatch repair proteins : a new aetiology for Sertoli cell-only syndrome. Mol Hum Reprod. 2003;9:61–8.

    Article  PubMed  CAS  Google Scholar 

  50. Tuttelmann F, Simoni M, Kliesch S, Ledig S, Dworniczak B, Tu F. Copy number variants in patients with severe oligozoospermia and Sertoli-cell-only syndrome. PLoS One. 2011;6:e19426.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Passe CMM, White CR, King MW, Quirk PL, Iovanna JL, Quirk CC. Loss of the Protein NUPR1 ( p8 ) Leads to delayed LHB expression , delayed ovarian maturation , and testicular development of a Sertoli-Cell-only syndrome-like phenotype in mice 1. Biol Reprod. 2008;79:598–607.

    Article  CAS  Google Scholar 

  52. Ni L, Xie H, Tan L, Province H. Multiple roles of FOXJ3 in spermatogenesis : a lesson from Foxj3 conditional. Mol Reprod Dev. 2016;83:1–21.

    Article  Google Scholar 

  53. Miyamoto T, Koh E, Tsujimura A, Miyagawa Y, Saijo Y, Namiki M, et al. Single-nucleotide polymorphisms in the LRWD1 gene may be a genetic risk factor for Japanese patients with Sertoli cell-only syndrome. Andrologia. 2012;46:273–6.

    Article  Google Scholar 

  54. Minase G, Miyamoto T, Miyagawa Y, Iijima M, Ueda H, Saijo Y, et al. Single-nucleotide polymorphisms in the human RAD21L gene may be a genetic risk factor for Japanese patients with azoospermia caused by meiotic arrest and Sertoli cell-only syndrome. Hum Fertil [Internet]. Informa UK Limited, trading as Taylor 8 Francis Group. 2017;0:000. https://doi.org/10.1080/14647273.2017.1292004.

    Article  CAS  Google Scholar 

  55. Miyamoto T, Shin T, Iijima M, Minase G, Okada H, Saijo Y, et al. The poly ( A ) polymerase beta gene may not be associated with azoospermia caused by Sertoli- cell-only syndrome in Japanese patients by comparing patients and normal controls. J Obstet Gynaecol (Lahore) [Internet]. Taylor & Francis. 2019;0:1–3. https://doi.org/10.1080/01443615.2018.1504205.

    Article  CAS  Google Scholar 

  56. Hayashi K, Chuva de Sousa Lopes SM, Kaneda M, Tang F, Hajkova P, Lao K, et al. MicroRNA biogenesis is required for mouse primordial germ cell development and spermatogenesis. PLoS One. 2008;3:1–9.

    Article  Google Scholar 

  57. Li W, Tan D, Zenali MJ, Brown RE. Constitutive activation of nuclear factor-kappa B (NF-κB) signaling pathway in fibrolamellar hepatocellular carcinoma. Int J Clin Exp Pathol. 2010;3:238–43.

    CAS  Google Scholar 

  58. Morris JK, Alberman E, Scott C, Jacobs P. Is the prevalence of Klinefelter syndrome increasing? Eur J Hum Genet. 2008;16:163–70.

    Article  PubMed  CAS  Google Scholar 

  59. Griffin DK, Finch KA. The genetic and cytogenetic basis of male infertility. Hum Fertil. 2005;8:19–26.

    Article  CAS  Google Scholar 

  60. Layman LC, Tho SPT, Clark AD, Kulharya A, McDonough PG. Phenotypic spectrum of 45,X/46,XY males with a ring Y chromosome and bilaterally descended testes. Fertil Steril. 2009;91:791–7.

    Article  PubMed  Google Scholar 

  61. Akinsal E, Baydilli N. Bayramov, Ruslan Ekmekcioglu O. A Rare Cause of Male Infertility : Urol Int. 2017;101:481–5.

    PubMed  Google Scholar 

  62. Gurbuz F, Ceylaner S, Erdogan S, Topaloglu AK, Yuksel B. Sertoli cell only syndrome with ambiguous genitalia. J Pediatr Endocrinol Metab. 2016;29:3–6.

    Article  Google Scholar 

  63. Foresta C, Moro E, Rossi A, Rossato M, Garolla A, Ferlin A. Role of the AZFa candidate genes in male infertility. J Endocrinol Invest. 2000;23:646–51.

    Article  PubMed  CAS  Google Scholar 

  64. Blagosklonova O, Fellmann F, Clavequin M, Roux C, Bresson J. AZFa deletions in Sertoli cell-only syndrome : a retrospective study. Mol Hum Reprod. 2000;6:795–9.

    Article  PubMed  CAS  Google Scholar 

  65. Fujisawa M, Shirakawa T, Kanzaki M. Y-chromosome microdeletion and phenotype in cytogenetically normal men with idiopathic azoospermia. Fertil Steril. 2001;76:491–5.

    Article  PubMed  CAS  Google Scholar 

  66. Hadjkacem-loukil L, Hadj-kacem H, Salem IH, Bahloul A, Fakhfakh F. Genotyping of Tunisian azoospermic men with Sertoli cell-only and maturation arrest. Andrologia. 2004:1–7.

  67. Yang Y, Ma MY, Xiao CY, Li L, Li SW, Zhang SZ. Massive deletion in AZFb / b + c and azoospermia with Sertoli cell only and / or maturation arrest. Int J Androl. 2007;6:573–8.

    Google Scholar 

  68. Weider K, Bergmann M, Giese S, Guillou F, Failing K, Brehm R. Altered differentiation and clustering of Sertoli cells in transgenic mice showing a Sertoli cell specific knockout of the connexin 43 gene. Differentiation [Internet]. Elsevier. 2011;82:38–49. https://doi.org/10.1016/j.diff.2011.03.001.

    Article  CAS  Google Scholar 

  69. Liang J, Wang N, He J, Du J, Guo Y, Li L, et al. Induction of Sertoli-like cells from human fibroblasts by NR5A1 and GATA4. Elife. 2019;8:1–27.

    Article  Google Scholar 

  70. Kasak L, Punab M, Nagirnaja L, Grigorova M, Minajeva A, Lopes AM, et al. Bi-allelic recessive loss-of-function variants in FANCM cause non-obstructive azoospermia. Am J Hum Genet [Internet]. ElsevierCompany. 2018;103:200–12. https://doi.org/10.1016/j.ajhg.2018.07.005.

    Article  CAS  Google Scholar 

  71. Sharrocks AD. The ETS-domain transcription factor family. Nat Rev Mol Cell Biol. 2001;2:827–37.

    Article  PubMed  CAS  Google Scholar 

  72. Castro-nallar E, Bacallao K, Parada-bustamante A, Madariaga M, Piottante A, Ebensperger M, et al. Androgen Receptor Gene CAG and GGN Repeat Polymorphisms. J Androl. 2010;31:552–9.

    Article  PubMed  CAS  Google Scholar 

  73. Yu C, Zhang Y-L, Pan W-W, Li X-M, Wang Z-W, Ge Z-J, et al. CRL4 complex regulates mammalian oocyte survival and reprogramming by activation of TET proteins (Science (2013) (1518)). Science (80- ). 2014;344:470.

    CAS  Google Scholar 

  74. Miyamoto T, Iijima M, Shin T, Minase G, Ueda H, Okada H, et al. CUL4B mutations are uncommon in Japanese patients with Sertoli-cell-only syndrome and azoospermia. J Obstet Gynaecol (Lahore) [Internet]. Informa UK Limited, trading as Taylor & Francis Group. 2017;0:1–2. https://doi.org/10.1080/01443615.2017.1336755.

    Article  CAS  Google Scholar 

  75. Faure AK, Kerjean A, Hazzouri M, Pelletier R, Pe M, Khochbin S, et al. Misregulation of histone acetylation in Sertoli cell-only syndrome and testicular cancer. Mol Hum Reprod. 2003;9:757–63.

    Article  PubMed  CAS  Google Scholar 

  76. Matsuyama S, Matsui F, Matsuoka K, Iijima M. Gonadal function and testicular histology in males with Prader - Willi syndrome. Endocrinol Diabetes Metab. 2018;2:1–8.

    Google Scholar 

  77. Bakker NE, Wolffenbuttel KP, Looijenga LHJ. Testes in Infants with Prader-Willi Syndrome : Human Chorionic Gonadotropin Treatment , Surgery and Histology. J Urol [Internet]. Elsevier Ltd. 2015;193:291–8. https://doi.org/10.1016/j.juro.2014.07.113.

    Article  CAS  Google Scholar 

  78. O’Bryan MK, Ph D, Grealy A, Sc B, Stahl PJ, Schlegel PN. Genetic variants in the ETV5 gene in fertile and infertile men with nonobstructive azoospermia associated with Sertoli cell – only syndrome. Fertil Steril [Internet]. Elsevier Inc. 2012;98:827-835.e3. https://doi.org/10.1016/j.fertnstert.2012.06.013.

    Article  CAS  Google Scholar 

  79. Colvin JS, Green RP, Schmahl J, Capel B, Ornitz DM. Male-to-Female Sex Reversal in Mice Lacking Fibroblast Growth Factor 9 the coelomic lining of the gonad (the coelomic epithe-lium) occurs between E11.3 and E12.1. This proliferation gives rise to Sertoli cells (a supporting cell lineage) early. Cell. 2001;104:875–89.

    Article  PubMed  CAS  Google Scholar 

  80. Chung C, Sc M, Lu C, Ph D, Cheng Y, Lin C, et al. Association of aberrant expression of sex-determining gene fi broblast growth factor 9 with Sertoli cell – only syndrome. Fertil Steril [Internet]. Elsevier Inc. 2013;100:1547-1554.e4. https://doi.org/10.1016/j.fertnstert.2013.08.004.

    Article  CAS  Google Scholar 

  81. Miyakawa H, Miyamoto T, Koh E, Tsujimura A, Miyagava Y, Saijo Y, et al. Single-nucleotide polymorphisms in the SEPTIN12 gene may be. 2012;33:483–7.

  82. Noveski P, Popovska-Jankovic K, Kubelka-Sabit K, Filipovski V, Lazarevski S, PT and P-KD. MicroRNA expression profiles in testicular biopsies of patients with impaired spermatogenesis. Andrology. 2016;4:1–8.

    Article  Google Scholar 

  83. Yao C, Sun M, Yuan Q, Niu M, Chen Z, Wang H, et al. MiRNA-133b promotes the proliferation of human Sertoli cells through targeting GLI3. Oncotarget. 2016;7:2201–19.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Yang C, Yao C, Tian R, Zhu Z, Zhao L, Li P, et al. miR-202-3p regulates Sertoli cell proliferation , synthesis function , and apoptosis by targeting LRP6 and cyclin D1 of Wnt / b -Catenin Signaling. Mol Ther Nucleic Acid [Internet]. Elsevier Ltd. 2019;14:1–19. https://doi.org/10.1016/j.omtn.2018.10.012.

    Article  CAS  Google Scholar 

  85. Li L, Zhang F, Liu S, Tian Y, Le F. Decreased expression of SAM68 in human testes with spermatogenic defects. Fertil Steril [Internet]. Elsevier Inc. 2014;102:61-67.e3. https://doi.org/10.1016/j.fertnstert.2014.03.036.

    Article  CAS  Google Scholar 

  86. Wollinal U, Schreiberl G, Gornigl M, Feldrappel S, Gabius MBH. Sertoli cell expression of galectin-l and -3 and accessible binding sites in normal human testis and Sertoli cell only-syndrome. Histol Histopathol. 1999;14:779–84.

    Google Scholar 

  87. Ruhui T, Chencheng Y, Chao Y, Zijue Z, Chong L, Erlei Z, et al. Fibroblast growth factor-5 promotes spermatogonial stem cell proliferation via ERK and AKT activation. Stem Cell Res Ther. 2019;10:1–14.

    Google Scholar 

  88. Sun T, Xin ÆZ, Jin ÆZ. Effect of TGF- b / Smad signaling on sertoli cell and possible mechanism related to complete sertoli cell-only syndrome. Mol Cell Biochem. 2008;319:1–7.

    Article  PubMed  CAS  Google Scholar 

  89. Hai Y, Sun M, Niu M, Yuan Q, Guo Y, Li Z, et al. BMP4 promotes human Sertoli cell proliferation via Smad1/5 and ID2/3 pathway and its abnormality is associated with azoospermia. Discov Med. United States. 2015;19:311–25.

    Google Scholar 

  90. Paduch DA, Hilz S, Grimson A, Schlegel PN, Jedlicka E, Wright WW. Aberrant gene expression by Sertoli cells in infertile men with Sertoli cell-only syndrome. PLoS One. 2019;14:1–27.

    Article  Google Scholar 

  91. Adly MA, Rezk M, Hussein A. Immunohistological profile of the ras homologous B Protein ( RhoB ) in human testes showing normal spermatogenesis , spermatogenic arrest and Sertoli cell only syndrome. Pathol Oncol Res. 2010;16:427–33.

    Article  PubMed  CAS  Google Scholar 

  92. Parada-Bustamante A, Molina C, Valencia C, Florez M, Lardone MC, Argandona F, 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;5:486–94.

    Article  PubMed  CAS  Google Scholar 

  93. Lan K, Chen Y, Chang C, Chang Y, Lin H. Up-regulation of SOX9 in Sertoli cells from testiculopathic patients accounts for increasing anti- mullerian hormone expression via impaired androgen receptor signaling. PLoS One. 2013;8:1–11.

    Article  Google Scholar 

  94. Lardone MC, Argandoña F, Flórez M, Parada-Bustamante A, Ebensperger M, Palma C, et al. Overexpression of CYP19A1 aromatase in Leydig cells is associated with steroidogenic dysfunction in subjects with Sertoli cell-only syndrome. Andrology. 2017;5:41–8.

    Article  PubMed  CAS  Google Scholar 

  95. Lardone MC, Argandoña F, Lorca M, Piottante A, Flórez M, Palma C, et al. Leydig cell dysfunction is associated with post-transcriptional deregulation of CYP17A1 in men with Sertoli cell-only syndrome. Mol Hum Reprod. 2018;24:203–10.

    Article  PubMed  CAS  Google Scholar 

  96. Fietz D, Bakhaus K, Wapelhorst B, Grosser G, Gu S, Kliesch S, et al. Membrane transporters for sulfated steroids in the human testis - cellular localization , expression pattern and functional analysis. PLoS One. 2013;8:e62638.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Rommerts FF, de Jong FH, Grootegoed JA, van der MHJ. Metabolic changes in testicular cells from rats after long-tern exposure to 37 degrees C in vivo or in vitro. J Endocrinol. 1980;85:471–9.

    Article  PubMed  CAS  Google Scholar 

  98. Hacker U, Schumann J, Göhde W, Müller K. Mammalian spermatogenesis as a biologic dosimeter for radiation. Acta Oncol (Madr). 1981;20:279–82.

    CAS  Google Scholar 

  99. Chowdhury I, Tharakan B, Bhat GK. Caspases - an update. Comp Biochem Physiol - B Biochem Mol Biol. 2008;151:10–27.

    Article  PubMed  Google Scholar 

  100. Almeida C, Correia S, Rocha E. Angela Alves, Luís Ferraz, Joquina Silva, Mário Sousa AB. Caspase signalling pathways in human spermatogenesis. J Assist Reprod Genet. 2013;4:487–95.

    Article  Google Scholar 

  101. Kim S, Yoon Y, Park Y. Involvement of the Fas – Fas ligand system and active caspase-3 in abnormal apoptosis in human testes with maturation arrest and Sertoli cell – only syndrome. Fertil Steril. 2007;87:547–53.

    Article  PubMed  CAS  Google Scholar 

  102. Lei B, Wan B, Peng J, Yang Y, Lv D, Zhou X, et al. PRPS2 expression correlates with Sertoli cell-only syndrome and inhibits the apoptosis of TM4 Sertoli cells. J Urol [Internet]. Elsevier Ltd. 2015;15:04078-1. https://doi.org/10.1016/j.juro.2015.04.116.

    Article  CAS  Google Scholar 

  103. Zhang H, Zhou D, Zhu F, Chen F, Zhu Y, Yu R, et al. Disordered APC / C - mediated cell cycle progression and IGF1 / PI3K / AKT signalling are the potential basis of Sertoli cell - only syndrome. Andrologia. 2019;51:1–8.

    Article  Google Scholar 

  104. Asbjørnsen G, Molne K, Klepp O, Aakvaag A. Testicular function after combination chemotherapy for Hodgkin’s disease. Scand J Haematol. 1976;16:66–9.

    Article  PubMed  Google Scholar 

  105. Rodriguez-Rigau LJ, Tcholakian RK, Smith KD, Steinberger E. In vitro steroid metabolic studies in human testes I: Effects of estrogen on progesterone metabolism. Steroids. United States. 1977;29:771–86.

    Article  CAS  Google Scholar 

  106. Mayerhofer A, Frungieri MB, Fritz S, Bulling A, Jessberger BVHJ. Evidence for catecholaminergic, neuronlike cells in the adult human testis: changes associated with testicular pathologies. J Androl. 1999;20:341–7.

    PubMed  CAS  Google Scholar 

  107. Gat Y, Gornish M, Perlow A, Chakraborty J, Levinger U, Pasqualotto F. Azoospermia and Sertoli-cell-only syndrome : hypoxia in the sperm production site due to impairment in venous drainage of male reproductive system. Andrologia. 2010;42:314–21.

    Article  PubMed  Google Scholar 

  108. Pajarinen JT, Karhunen PJ. Spermatogenic arrest and “Sertoli cell-only” syndrome- common alcohol-induced disorders of the human testis. Int J Androl. 1994;17:292–9.

    Article  PubMed  CAS  Google Scholar 

  109. Liu J, Ding D, Liu J. Varicocele-caused progressive damage in bilateral testis and Sertoli Cell-only syndrome in homolateral testis in rats. Med Sci Monit. 2014;20:1931–6.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Pei G, Youngf H, Goldstein M, Phillips DM, Sundaram K, Gunsalus GL, et al. Sertoli Cell-only syndrome produced by cold testicular. Endocrinology. 1988;122:3–4.

    Google Scholar 

  111. Schoor RA, Elhanbly S, Niederberger CS, Ross LS. The role of testicular biopsy in the modern management of male infertility. J Urol. 2002;167:197–200.

    Article  PubMed  Google Scholar 

  112. Bettocchp C, Parkinson MC, Ralph DJ, Pryor JP. Clinical aspects associated with Sertoli-cell-only histology. Br J Urol. 1998;82:534–7.

    Article  Google Scholar 

  113. Tyler-Smith C, Krausz C. The will-o’-the-wisp of genetics—hunting for the azoospermia factor gene. N Engl J Med. Europe PMC Funders. 2009;360:925.

    Article  CAS  Google Scholar 

  114. Paulis G, Paulis L, Concas C, Di Sarno M, Pagano R, Di Filippo A, et al. Pregnancy and live birth after follicle-stimulating hormone treatment for an infertile couple including a male affected by Sertoli cell-only syndrome. Res Reports Urol. 2017;9:203–8.

    Article  Google Scholar 

  115. Ustuner M, Yilmaz H, Yavuz U, Ciftci S, Saribacak A, Aynur BS, et al. Varicocele repair improves testicular histology in men with nonobstructive azoospermia. Biomed Res Int. 2015;2015:1–6.

    Article  Google Scholar 

  116. Pasqualotto FF, Sobreiro BP, Hallak J, Pasqualotto EB, Lucon AM. Induction of spermatogenesis in azoospermic men after varicocelectomy repair: an update. Fertil Steril. Elsevier. 2006;85:635–9.

    Article  Google Scholar 

  117. Lee JS, Park HJ, Seo JT. What is the indication of varicocelectomy in men with nonobstructive azoospermia? Urology. Elsevier. 2007;69:352–5.

    Google Scholar 

  118. Kadioǧlu A, Tefekli̇ A, Cayan S, Kandirali E, Erdemi̇r F, Tellaloǧlu S. Microsurgical inguinal varicocele repair in azoospermic men. Urology. Elsevier; 2001;57:328–333.

  119. Cakan M, Altuğ U. Induction of spermatogenesis by inguinal varicocele repair in azoospermic men. Arch Androl. Taylor & Francis. 2004;50:145–50.

    Article  CAS  Google Scholar 

  120. Esteves SC, Glina S. Recovery of spermatogenesis after microsurgical subinguinal varicocele repair in azoospermic men based on testicular histology. Int braz j urol. SciELO Brasil. 2005;31:541–8.

    Google Scholar 

  121. Esteves SC, Agarwal A. Re: Sperm retrieval rates and intracytoplasmic sperm injection outcomes for men with non-obstructive azoospermia and the health of resulting offspring. Asian J Androl [Internet]. 2014/04/22. Medknow Publications & Media Pvt Ltd; 2014;16:642. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104100/

  122. Tournaye H, Verheyen G, Nagy P, Ubaldi F, Goossens A, Silber S, et al. Are there any predictive factors for successful testicular sperm recovery in azoospermic patients? Hum Reprod. England. 1997;12:80–6.

    CAS  Google Scholar 

  123. Mancini M, Carmignani L, Gazzano G, Sagone P, Gadda F, Bosari S, et al. High prevalence of testicular cancer in azoospermic men without spermatogenesis. Hum Reprod. 2007;22:1042–6.

    Article  PubMed  CAS  Google Scholar 

  124. Schlegel PN. Testicular sperm extraction : microdissection improves sperm yield with minimal tissue excision. Hum Mol Genet. 1999;14:131–5.

    CAS  Google Scholar 

  125. Eliveld J, van Wely M, Meißner A, Repping S, van der Veen F, van Pelt AMM. The risk of TESE-induced hypogonadism: a systematic review and meta-analysis. Hum Reprod Update. Oxford University Press. 2018;24:442–54.

    Article  Google Scholar 

  126. Esteves SC, Varghese AC. Laboratory handling of epididymal and testicular spermatozoa: what can be done to improve sperm injections outcome. J Hum Reprod Sci. Wolters Kluwer--Medknow Publications. 2012;5:233.

    Article  Google Scholar 

  127. Deruyver Y, Vanderschueren D, Van der Aa F. Outcome of microdissection TESE compared with conventional TESE in non-obstructive azoospermia : a systematic review. Andrology. 2013;2:20–4.

    Article  PubMed  Google Scholar 

  128. Gul U, Turunc T, Haydardedeoglu B, Yaycioglu O, Kuzgunbay B. Sperm retrieval and live birth rates in presumed Sertoli-cell-only syndrome in testis biopsy : a single centre experience. Andrology. 2013;1:47–51.

    Article  PubMed  CAS  Google Scholar 

  129. Modarresi T, Sc M, Hosseinifar H, Sc M, Hampa AD, Chehrazi M, et al. Predictive factors of successful microdissection testicular sperm extraction in patients with presumed Sertoli cell-only syndrome. Int J Fertil Steril. 2013;9:107–12.

    Google Scholar 

  130. Yamamoto Y, Sofikitis N, Mio Y, Miyagawa I. Highly sensitive quantitative telomerase assay of diagnostic testicular biopsy material predicts the presence of haploid spermatogenic cells in therapeutic testicular biopsy in men with Sertoli cell-only syndrome. Hum Reprod. 1999;14:3041–7.

    Article  PubMed  CAS  Google Scholar 

  131. Berookhim BMGDP, Zaninovic N, Rosenwaks Z, Peter N, Schlegel M. Microdissection testicular sperm extraction in men with sertoli cell only testicular histology. Fertil Steril. 2014;102:1282–6.

    Article  PubMed  PubMed Central  Google Scholar 

  132. Yu Y, Xi Q, Wang R, Zhang H. Intraoperative assessment of tubules in predicting microdissection testicular sperm extraction outcome in men with Sertoli cell-only syndrome. J Int Med Res. 2018;47:722–9.

    Article  PubMed  PubMed Central  Google Scholar 

  133. Aponte PM, Schlatt IIS, Luiz III, De Franca R. Biotechnological approaches to the treatment of aspermatogenic men. Clinics. 2013;68(S1):157–67.

    Article  PubMed  PubMed Central  Google Scholar 

  134. Wang X, Xie S, Li Z, Ye Z, Gu X, Zhou L, et al. Generation of an iPSC line ( HUSTi002-A ) from fi broblasts of a patient with Sertoli cell-only syndrome carrying c . 731 _ 732delAT in PIWIL2 gene. Stem Cell Res [Internet]. Elsevier. 2020;42:101703. https://doi.org/10.1016/j.scr.2020.101703.

    Article  CAS  Google Scholar 

  135. Li J, Guo W, Li F, He J, Yu Q, Wu X, et al. HnRNPL as a key factor in spermatogenesis : Lesson from functional proteomic studies of azoospermia patients with sertoli cell only syndrome ☆. J Proteomics [Internet]. Elsevier B.V. 2012;75:2879–91. https://doi.org/10.1016/j.jprot.2011.12.040.

    Article  CAS  Google Scholar 

  136. Alikhani M, Ali M, Gilani S, Zabet-moghaddam M, Parker L, Wo Y, et al. Quantitative proteomic analysis of human testis reveals system-wide molecular and cellular pathways associated with non-obstructive azoospermia. J Proteomics [Internet]. Failure:Problem in retrieving ISSN for S1874391917300568. 2017. https://doi.org/10.1016/j.jprot.2017.02.007.

  137. Yu Q, Gu X, Shang X, Li H, Xiong C. Discrimination and characterization of Sertoli cell-only syndrome in non-obstructive azoospermia using cell-free seminal DDX4. Reprod Biomed Online [Internet]. Elsevier Ltd. 2016. https://doi.org/10.1016/j.rbmo.2016.05.001.

  138. Abofoul-azab M, Lunenfeld E, Levitas E, Zeadna A. Identification of Premeiotic, Meiotic, and Postmeiotic Cells in Testicular Biopsies Without Sperm from Sertoli Cell-Only Syndrome Patients. Int J Mol Sci. 2019;20:470.

    Article  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mehdi Abbasi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ghanami Gashti, N., Sadighi Gilani, M.A. & Abbasi, M. Sertoli cell-only syndrome: etiology and clinical management. J Assist Reprod Genet 38, 559–572 (2021). https://doi.org/10.1007/s10815-021-02063-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-021-02063-x

Keywords

Navigation