Skip to main content
Springer Nature Link
Log in

Differentiation markers of Sertoli cells and germ cells in fetal and early postnatal human testis

  • Original Article
  • Published:
Anatomy and Embryology Aims and scope Submit manuscript

Abstract

The definition of the temporal sequence of appearance of fetal markers during prenatal and early postnatal development in Sertoli and germ cells may be important for understanding the mechanisms underlying their reexpression in disorders of the adult testis. For this reason, we studied the expression of Sertoli and germ cell markers in 25 human testes spanning a period from 8 gestational weeks to 4 years. Well-characterized antibodies were employed to anti-Müllerian hormone (AMH), cytokeratin 18 (CK18), vimentin (VIM), M2A-antigen (M2A), germ cell alkaline phosphatase (GCAP), and somatic angiotensin-converting enzyme (sACE) on formalin-fixed and microwave-pretreated paraffin sections. In Sertoli cells, AMH and VIM were consistently present. While VIM and CK18 were coexpressed in embryonic testes, CK18 was progressively downregulated and completely absent from the 20th gestational week. M2A was absent or moderately expressed in fetal Sertoli cells but increased during further development. In germ cells, M2A was consistently found in primordial germ cells (PGCs) as well as in M- and T1-prespermatogonia. In contrast, sACE and GCAP were absent from PGCs but were a distinct feature of late M- and early T1-prespermatogonia and appeared predominantly between the 18th and the 22nd gestational weeks. Both T2-prespermatogonia and postnatal prespermatogonia were devoid of any marker. While CK18 represents a differentiation marker for fetal Sertoli cells, M2A, GCAP, and sACE can be used as differentiation markers for the discrimination of different germ cell types during human prespermatogenesis. Because various immunophenotypes reflect distinct differentiation stages, this knowledge may be important for understanding adult testicular pathology.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
€32.70 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Finland)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Armstrong GR, Buckley CH, Kelsey AM (1991) Germ cell expression of placental alkaline phosphatase in male pseudohermaphroditism. Histopathology 18:541–547

    CAS  PubMed  Google Scholar 

  • Bailey D, Marks A, Stratis M, Baumal R (1991) Immunohistochemical staining of germ cell tumors and intratubular malignant germ cells of the testis using antibody to placental alkaline phosphatase and a monoclonal anti seminoma antibody. Mod Pathol 4:167–171

    CAS  PubMed  Google Scholar 

  • Baker ML, Metcalfe SA, Hutson JM (1990) Serum levels of Müllerian inhibiting substance in boys from birth to 18 years, as determined by enzyme immunoassay. J Clin Endocrinol Metab 70:11–15

    CAS  PubMed  Google Scholar 

  • Baumal R, Bailey D, Giwercman A, Skakkebaek N, Stratis M, Marks A (1989) A novel maturation marker for human Sertoli cells. Int J Androl 12:354–359

    CAS  PubMed  Google Scholar 

  • Bergmann M, Kliesch S (1994) The distribution pattern of cytokeratin and vimentin immunoreactivity in testicular biopsies of infertile men. Anat Embryol 190:515–520

    Article  CAS  PubMed  Google Scholar 

  • Burke AP, Mostofi FK (1988) Placental alkaline phosphatase immunohistochemistry of intratubular malignant germ cells and associated testicular germ cell tumors. Hum Pathol 19:663–670

    CAS  PubMed  Google Scholar 

  • Cheville JC, Rao S, Iczkowski KA, Lohse CM, Pankratz VS (2000) Cytokeratin expression in seminoma of the human testis. Am J Clin Pathol 113:583–588

    Article  CAS  PubMed  Google Scholar 

  • deMiguel MP, Bethencourt FR, Arenas MI, Fraile B, Paniagua R (1997) Intermediate filaments in the Sertoli cells of the ageing human testis. Virch Arch 431:131–138

    Article  CAS  Google Scholar 

  • Francavilla S, Cordeschi G, Properzi G, Concordia N, Cappa F, Pozzi V (1990) Ultrastructure of fetal human gonad before sexual differentiation and during early testicular and ovarian development. J Submicrosc Cytol Pathol 22:389–400

    CAS  PubMed  Google Scholar 

  • Franke FE, Pauls K, Kerkman L, Steger K, Klonisch T, Metzger R, Alhenc-Gelas F, Burkhardt E, Bergmann M, Danilov SM (2000) Somatic isoform of angiotensin I-converting enzyme in the pathology of testicular germ cell tumors. Hum Pathol 31:1466–1476

    Article  CAS  PubMed  Google Scholar 

  • Fukuda T, Hedinger C, Groscurth P (1975) Ultrastructure of developing germ cells in the fetal human testis. Cell Tissue Res 161:55–70

    Article  CAS  PubMed  Google Scholar 

  • Gaskell TL, Esnal A, Robinson LLL, Anderson RA, Saunders PTK (2004) Immunohistochemical profiling of germ cells within the human fetal testis: identification of three subpopulations. Biol Reprod, in press

    Google Scholar 

  • Giwercman A, Cantell L, Marks A (1991) Placental-like alkaline phosphatase as a marker of carcinoma-in-situ of the testis. Comparison with monoclonal antibodies M2A and 43–9F. APMIS 99:586–594

    CAS  PubMed  Google Scholar 

  • Heyn R, Makabe S, Motta PM (1998) Ultrastructural dynamics of human testicular cords from 6 to 16 weeks of embryonic development. Study by transmission and high resolution scanning electron microscopy. Ital J Anat Embryol 103 (suppl. 1):17–29

    Google Scholar 

  • Hilscher W (1991) The genetic control and germ cell kinetics of the female and male germ line in mammals including man. Hum Reprod 6:1416–1425

    CAS  PubMed  Google Scholar 

  • Hofmann MC, Millan JL (1993) Developmental expression of alkaline phosphatase genes; reexpression in germ cell tumours and in vitro immortalized germ cells. Eur Urol 23:38–44

    CAS  PubMed  Google Scholar 

  • Hudson PL, Dougas I, Donahoe PK, Cate RL, Epstein J, Pepinsky RB, McLaughlin DT (1990) An immunoassay to detect human Müllerian inhibiting substance in males and females during development. J Clin Endocrinol Metab 70:16–22

    CAS  PubMed  Google Scholar 

  • Hustin J, Collette J, Franchimont P (1987) Immunohistochemical demonstration of placental alkaline phosphatase in various states of testicular development and in germ cell tumours. Int J Androl 10:29–35

    CAS  PubMed  Google Scholar 

  • Hustin J, Gillerot Y, Collette J, Franchimont P (1990) Placental alkaline phosphatase in developing normal and abnormal gonads and in germ-cell tumours. Virchows Archiv A Pathol Anat 417:67–72

    CAS  Google Scholar 

  • Jacobsen GK, Norgaard-Pedersen B (1984) Placental alkaline phosphatase in testicular germ cell tumours and in carcinoma-in-situ of the testis: an immunohistochemical study. Acta Pathol Microbiol Immunol Scand A 92:323–329

    CAS  PubMed  Google Scholar 

  • Jorgensen N, Giwercman A, Muller J, Skakkebaek NE (1993) Immunohistochemical markers of carcinoma in situ of the testis also expressed in normal infantile germ cells. Histopathol 22:373–378

    CAS  Google Scholar 

  • Jorgensen N, Rajpert-de Meyts E, Graem N, Müller J, Giwercman A, Skakkebaek NE (1995) Expression of immunohistochemical markers for testicular carcinoma in situ by normal human fetal germ cells. Lab Invest 72:223–231

    CAS  PubMed  Google Scholar 

  • Josso N, Legeai L, Forest MG, Chaussain JL, Brauner R (1990) An enzyme linked immunoassay for anti-Müllerian hormone: a new tool for the evaluation of testicular function in infants and children. J Clin Endocrinol Metab 70:23–27

    CAS  PubMed  Google Scholar 

  • Kliesch S, Behre HM, Hertle L, Bergmann M (1998) Alteration of Sertoli cell differentiation in the presence of carcinoma in situ in human testis. J Urol 160:1894–1898

    Article  CAS  PubMed  Google Scholar 

  • Lee MM, Donahoe PK, Hasegawa T, Silvermann B, Crist GB, Best S, Hasegawa Y, Noto RA, Schoenfeld D, MacLaughlin DT (1996) Muellerian inhibiting substance in humans: normal levels from infancy to adulthood. J Clin Endocrinol Metab 81:571–576

    Article  CAS  PubMed  Google Scholar 

  • Marks A, Sutherland DR, Bailey D, Iglesias J, Law J, Lei M, Yeger H, Banerjee D, Baumal, R (1999) Characterization and distribution of an oncofetal antigen (M2A antigen) expressed on testicular germ cell tumours. Br J Cancer 80:569–578

    Article  CAS  PubMed  Google Scholar 

  • McKay DG, Hertig AT, Adams EC, Danzinger S (1953) Histochemical observations on the germ cells of human embryos. Anat Rec 117:201–219

    CAS  PubMed  Google Scholar 

  • Miettinen M, Virtanen I, Talerman A (1985) Intermediate filament proteins in human testis and testicular germ-cell tumors. Am J Pathol 120:402–410

    CAS  PubMed  Google Scholar 

  • Pauls K, Fink L, Franke FE (1999) Angiotensin-converting enzyme (CD143) in neoplastic germ cells. Lab Invest 79:1425–1435

    CAS  PubMed  Google Scholar 

  • Rajpert-de Meyts E, Jorgensen N, Graem N, Müller J, Cate RL, Skakkebaek NE (1999) Expression of anti-Müllerian hormone during normal and pathological gonadal development: association with differentiation of Sertoli and granulosa cells. J Clin Endocrinol Metabol 84:3836–3844

    Article  Google Scholar 

  • Rajpert-De Meyts E, Bartkova J, Samson M, Hoei-Hansen CE, Frydelund-Larsen L, Bartek J, Skakkebaek NE (2003) The emerging phenotype of the testicular carcinoma in situ germ cell. APMIS 111:267–279

    Article  PubMed  Google Scholar 

  • Rey R, Al-Attar L, Louis F, Jaubert F, Barbet P, Nihoul-Fékété C, Josso N (1996) Testicular dysgenesis does not affect expression of anti-Müllerian hormone by Sertoli cells in pre-meiotic seminiferous tubules. Am J Pathol 148:1689–1698

    CAS  PubMed  Google Scholar 

  • Rey R, Sabourin JC, Venara M, Long WQ, Jaubert F, Zeller WP, Duvillard P, Chemes H, Bidart JM (2000) Anti-Muellerian hormone is a specific marker of Sertoli- and granulosa-cells in gonadal tumors. Hum Pathol 31:1202–1208

    Article  CAS  PubMed  Google Scholar 

  • Rogatsch H, Jezek D, Hittmair A, Mikuz G, Feichtinger H (1996) Expression of vimentin, cytokeratin, and desmin in Sertoli cells of human fetal, cryptorchid, and tumour-adjacent testicular tissue. Virch Arch 427:497–502

    CAS  Google Scholar 

  • Romeo R, Castorina S, Marcello MF (1995) Intermediate filaments of human Sertoli cells in germinal alterations. Ital J Anat Embryol 100:75–81

    CAS  Google Scholar 

  • Skakkebaek NE, Berthelsen JG, Giwercman A, Müller J (1987) Carcinoma-in-situ of the testis: possible origin from gonocytes and precursor of all types of germ cell tumours except spermatocytoma. Int J Androl 10:19–28

    CAS  PubMed  Google Scholar 

  • Skakkebaek NE, Rajpert-de Meyts E, Jorgensen N, Carlsen E, Petersen PM, Giwercman A, Andersen AG, Jensen TK, Andersson AM, Muller J (1998) Germ cell cancer and disorders of spermatogenesis: an environmental connection? APMIS 106:3–11

    CAS  PubMed  Google Scholar 

  • Soosay GN, Bobrow L, Happerfield L, Parkinson MC (1991) Morphology and immunohistochemistry of carcinoma in situ adjacent to testicular germ cell tumours in adults and children: implications for histogenesis. Histopathology 19:517–544

    Google Scholar 

  • Steger K, Rey R, Kliesch S, Louis F, Schleicher G, Bergmann M (1996) Immunohistochemical detection of immature Sertoli cell markers in testicular tissue of infertile men: a preliminary study. Int J Androl 19:122–128

    CAS  PubMed  Google Scholar 

  • Steger K, Rey R, Louis F, Kliesch S, Behre HM, Nieschlag E, Hoepffner W, Bailey D, Marks A, Bergmann M (1999) Reversion of the differentiated phenotype and maturation block in Sertoli cells in pathological human testis. Hum Reprod 14:136–143

    Article  CAS  PubMed  Google Scholar 

  • Stosiek P, Kasper M, Karsten U (1990) Expression of cytokeratins 8 and 18 in human Sertoli cells of immature and atrophic seminiferous tubules. Differentiation 43:66–70

    CAS  PubMed  Google Scholar 

  • Tran D, Picard JY, Campargue J, Josso N (1987) Immunocytochemical detection of anti-Müllerian hormone in Sertoli cells of various mammalian species including human. J Histochem Cytochem 35:733–743

    CAS  PubMed  Google Scholar 

  • Voutilainen R (1992) Differentiation of the fetal gonad. Horm Res 38 (suppl. 2):66–71

  • Wartenberg H (1981) Differentiation and development of the testis. In: Burger H, de Kretser D (eds) The testis. Raven Press, New York, pp 39–80

Download references

Acknowledgements

The skillful technical assistance of Jutta Dern-Wieloch, Gerlinde Erhardt, Alexandra Hax, and Anne Hild, Institute of Veterinary Anatomy of the University of Giessen, is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Institute of Pathology, University of Giessen, Germany

    Folker E. Franke & Katharina Pauls

  2. Institute of Pathology, University of Bonn, Germany

    Katharina Pauls

  3. Centro de Investigaciones Endocrinológicas (CONICET), Hospital de Ninos R Gutiérrez and Department of Histology, Embryology and Cell Biology, School of Medicine, University of Buenos Aires, Argentina

    Rodolfo Rey

  4. Banting and Best Institute of Medical Research, University of Toronto, Canada

    Alexander Marks

  5. Institute of Veterinary Anatomy, Histology and Embryology, University of Giessen, Germany

    Martin Bergmann

  6. Klinik für Urologie und Kinderurologie, Rudolf-Buchheim-Strasse 7, 35385 , Giessen, Germany

    Klaus Steger

  7. Department of Urology and Pediatric Urology, University of Giessen, Germany

    Klaus Steger

Authors
  1. Folker E. Franke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katharina Pauls
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rodolfo Rey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alexander Marks
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Martin Bergmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Klaus Steger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Klaus Steger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Franke, F.E., Pauls, K., Rey, R. et al. Differentiation markers of Sertoli cells and germ cells in fetal and early postnatal human testis. Anat Embryol 209, 169–177 (2004). https://doi.org/10.1007/s00429-004-0434-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00429-004-0434-x

Keywords

Search

Navigation