Skip to main content
SpringerLink
Log in

The role of gonadotrophins in gonocyte transformation during minipuberty

  • Original Article
  • Published:
Pediatric Surgery International Aims and scope Submit manuscript

Abstract

Purpose

Postnatal surge of gonadotrophins, Luteinizing hormone (LH) and Follicle-Stimulating hormone (FSH) known as minipuberty, is critical for gonocyte maturation into spermatogonial stem cells (SSC) in the testis. Gonadotrophins are essential for optimum fertility in men, but very little is known how they regulate germ cells during minipuberty. This study examined whether gonadotrophins play a role on gonocyte transformation in vivo.

Methods

Testes from hypogonadal (hpg) mice and their wild type (WT) littermates (n = 6/group) were weighed, and processed in paraffin at postnatal days (D) 0, 3, 6 and 9. Mouse VASA homologue (germ cell marker), anti-Müllerian hormone (Sertoli cell marker) antibodies and DAPI (nuclei marker) were used for immunofluorescence followed by confocal imaging. Germ cells on or off basement membrane (BM) and Sertoli cells/tubule were counted using Image J and analyzed with GraphPad.

Results

Comparing to WT littermates, there were significantly fewer germ cells on BM/tubule (p < 0.05) in D9 hpg mice, whereas there was no significant difference for germ cells off BM/tubule and Sertoli cells/tubule between littermates. However, testicular weight was significantly reduced in D3-D9 hpg mice comparing to WT littermates.

Conclusion

Gonadotrophin deficiency reduced D9 germ cells on BM indicating impaired gonocyte transformation into SSC. This suggests that gonadotrophins may mediate gonocyte transformation during minipuberty.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Hutson JM, Southwell BR, Li R, Lie G, Ismail K, Harisis G, Chen N (2013) The regulation of testicular descent and the effects of cryptorchidism. Endocr Rev 34(5):725–752

    Article  CAS  PubMed  Google Scholar 

  2. Hadziselimovic F, Huff D, Duckett J, Herzog B, Elder J, Snyder H, Buser M (1987) Treatment of cryptorchidism with low doses of buserelin over a 6-months period. Eur J Pediatr 146(2):S56–S58

    Article  PubMed  Google Scholar 

  3. Li R, Vannitamby A, Yue SSK, Handelsman D, Hutson J (2017) Mouse minipuberty coincides with gonocyte transformation into spermatogonial stem cells: a model for human minipuberty. Reprod Fertil Dev 29(12):2430–2436

    Article  CAS  PubMed  Google Scholar 

  4. Hadziselimovic F, Zivkovic D, Bica DT, Emmons LR (2005) The importance of mini-puberty for fertility in cryptorchidism. J Urol 174(4):1536–1539

    Article  PubMed  Google Scholar 

  5. Cortes D, Thorup J, Beck BL (1995) Quantitative histology of germ cells in the undescended testes of human fetuses, neonates and infants. J Urol 154(3):1188–1192

    Article  CAS  PubMed  Google Scholar 

  6. Li R, Vannitamby A, Meijer J, Southwell B, Hutson J (2015) Postnatal germ cell development during mini-puberty in the mouse does not require androgen receptor: implications for managing cryptorchidism. J Urol 193(4):1361–1367. https://doi.org/10.1016/j.juro.2014.10.024

    Article  CAS  PubMed  Google Scholar 

  7. Su S, Szarek M, Vooght A, Hutson J, Li R (2014) Gonocyte transformation to spermatogonial stem cells occurs earlier in patients with undervirilisation syndromes. J Pediatr Surg 49(2):323–327. https://doi.org/10.1016/j.jpedsurg.2013.11.047

    Article  PubMed  Google Scholar 

  8. Li R, Thorup J, Sun C, Cortes D, Southwell B, Hutson J (2014) Immunofluorescent analysis of testicular biopsies with germ cell and sertoli cell markers shows significant MVH negative germ cell depletion with older age at orchiopexy. J Urol 191(2):458–464

    Article  PubMed  Google Scholar 

  9. Loebenstein M, Thorup J, Cortes D, Clasen-Linde E, Hutson JM, Li R (2019) Cryptorchidism, gonocyte development, and the risks of germ cell malignancy and infertility: a systematic review. J Pediatr Surg. https://doi.org/10.1016/j.jpedsurg.2019.06.023

    Article  PubMed  Google Scholar 

  10. Singh J, Handelsman D (1996) Neonatal administration of FSH increases Sertoli cell numbers and spermatogenesis in gonadotropin-deficient (hpg) mice. J Endocrinol 151(1):37–48

    Article  CAS  PubMed  Google Scholar 

  11. O’shaughnessy P, Monteiro A, Verhoeven G, De Gendt K, Abel M (2010) Effect of FSH on testicular morphology and spermatogenesis in gonadotrophin-deficient hypogonadal mice lacking androgen receptors. Reproduction 139(1):177–184

    Article  PubMed  PubMed Central  Google Scholar 

  12. Singh J, Handelsman DJ (1996) The effects of recombinant FSH on testosterone-induced spermatogenesis in gonadotrophin-deficient (hpg) mice. J Androl 17(4):382–393

    CAS  PubMed  Google Scholar 

  13. Abel MH, Wootton AN, Wilkins V, Huhtaniemi I, Knight PG, Charlton HM (2000) The effect of a null mutation in the follicle-stimulating hormone receptor gene on mouse reproduction. Endocrinology 141(5):1795–1803

    Article  CAS  PubMed  Google Scholar 

  14. Kumar TR, Wang Y, Lu N, Matzuk MM (1997) Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nat Genet 15(2):201

    Article  CAS  PubMed  Google Scholar 

  15. Dierich A, Sairam MR, Monaco L, Fimia GM, Gansmuller A, LeMeur M, Sassone-Corsi P (1998) Impairing follicle-stimulating hormone (FSH) signaling in vivo: targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance. Proc Natl Acad Sci 95(23):13612–13617

    Article  CAS  PubMed  Google Scholar 

  16. Singh J, O’Neill C, Handelsman DJ (1995) Induction of spermatogenesis by androgens in gonadotropin-deficient (hpg) mice. Endocrinology 136(12):5311–5321

    Article  CAS  PubMed  Google Scholar 

  17. Cattanach B, IDDON CA, Charlton H, CHIAPPA SA, Fink G (1977) Gonadotrophin-releasing hormone deficiency in a mutant mouse with hypogonadism. Nature 269(5626):338

    Article  CAS  PubMed  Google Scholar 

  18. Allan CM, Garcia A, Spaliviero J, Zhang F-P, Jimenez M, Huhtaniemi I, Handelsman DJ (2004) Complete Sertoli cell proliferation induced by follicle-stimulating hormone (FSH) independently of luteinizing hormone activity: evidence from genetic models of isolated FSH action. Endocrinology 145(4):1587–1593

    Article  CAS  PubMed  Google Scholar 

  19. Plant T (2008) Hypothalamic control of the pituitary-gonadal axis in higher primates: key advances over the last two decades. J Neuroendocrinol 20(6):719–726

    Article  CAS  PubMed  Google Scholar 

  20. Li R, Vannitamby A, Zhang JG, Fehmel EL, Southwell BR, Hutson JM (2015) Oct4-GFP expression during transformation of gonocytes into spermatogonial stem cells in the perinatal mouse testis. J Pediatr Surg 50(12):2084–2089. https://doi.org/10.1016/j.jpedsurg.2015.08.031

    Article  PubMed  Google Scholar 

  21. Li R, Azzollini D, Shen R, Thorup J, Clasen-Linde E, Cortes D, Hutson JM (2019) Postnatal germ cell development during first 18 months of life in testes from boys with non-syndromic cryptorchidism and complete or partial androgen insensitivity syndrome. J Pediatr Surg 54(8):1654–1659. https://doi.org/10.1016/j.jpedsurg.2018.12.011

    Article  PubMed  Google Scholar 

  22. Baker PJ, O’Shaughnessy PJ (2001) Role of gonadotrophins in regulating numbers of Leydig and Sertoli cells during fetal and postnatal development in mice. Reproduction 122(2):227–234

    Article  CAS  PubMed  Google Scholar 

  23. Myers M, Ebling FJP, Nwagwu M, Boulton R, Wadhwa K, Stewart J, Kerr JB (2005) Atypical development of Sertoli cells and impairment of spermatogenesis in the hypogonadal (hpg) mouse. J Anat 207(6):797–811. https://doi.org/10.1111/j.1469-7580.2005.00493.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Heckert LL, Griswold MD (2002) The expression of the follicle-stimulating hormone receptor in spermatogenesis. Recent Prog Horm Res 57:129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Abel M, Baker P, Charlton H, Monteiro A, Verhoeven G, De Gendt K, Guillou F, O’Shaughnessy P (2008) Spermatogenesis and sertoli cell activity in mice lacking sertoli cell receptors for follicle-stimulating hormone and androgen. Endocrinology 149(7):3279–3285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We sincerely thank Prof. David Handelsman from Andrology Laboratory, ANZAC Research Institute, Concord Hospital, University of Sydney, Australia, for kind supply of the initial frozen sperm of hpg mice and other technical assistance to enable the establishment of this strain at our institute.

Funding

This study was funded by the Australian National Health and Medical Research Council (Grant no. APP1127109) and the Victorian Government’s Operational Infrastructure Support Program.

Author information

Authors and Affiliations

  1. Douglas Stephens Surgical Research Group, Murdoch Children’s Research Institute, The Royal Children’s Hospital, Melbourne, Australia

    Emily Burton, Sanduni Amaya Abeydeera, Gulcan Sarila, Shengde Wu, Melissa Yixin Tien, John Hutson & Ruili Li

  2. Department of Pediatrics, University of Melbourne, Melbourne, Australia

    Emily Burton, Melissa Yixin Tien, John Hutson & Ruili Li

  3. Biological Optical Microscopy Platform, The University of Melbourne, Melbourne, Australia

    Hyun-Jung Cho

  4. Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China

    Shengde Wu

  5. Department of Urology, The Royal Children’s Hospital, Melbourne, Australia

    John Hutson

Authors
  1. Emily Burton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sanduni Amaya Abeydeera
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gulcan Sarila
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hyun-Jung Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shengde Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Melissa Yixin Tien
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. John Hutson
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ruili Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

EB performed experiments, analyzed data and wrote the first draft, HJC created the macro for cell counting, SAA and SW collected testes and prepared the paraffin blocks, GS and MYT provided assistance on data analysis and figure preparation. RL conceived the study and did the initial critical edition followed by JH’s critical revision. None of the authors has any potential conflict of interest to disclose.

Corresponding author

Correspondence to Ruili Li.

Ethics declarations

Conflict of interest

Author RL and JH have received the above mentioned research grant. Authors EB, SAA, GS, SW, MYT, JH, and RL declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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

Burton, E., Abeydeera, S.A., Sarila, G. et al. The role of gonadotrophins in gonocyte transformation during minipuberty. Pediatr Surg Int 36, 1379–1385 (2020). https://doi.org/10.1007/s00383-020-04737-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00383-020-04737-6

Keywords

Search

Navigation