Successful testicular sperm recovery and IVF treatment in a man with Leydig cell hypoplasia

  • M. E. Bakircioglu
  • P. Tulay
  • N. Findikli
  • B. Erzik
  • M. Gultomruk
  • M. Bahceci


Fetal sex differentiation of the male involves complex processes and is dependent on the androgen production from fetal Leydig cells triggered by placental human chorionic gonadotropin (hCG) [1, 2]. It is later replaced by luteinizing hormone (LH) that is secreted by the fetal pituitary gland during gestation [3]. The hormones, such as antimullerian hormone (AMH) synthesized by Sertoli cells of the testes, testosterone produced by the Leydig cells and dihydrotestosterone, are also essential for the formation of male genitalia [4, 5, 6]. Because the action of both hCG and LH is through the luteinizing hormone/chorionic gonadotropin receptor (LHCGR), its presence and smooth function is crucial for male sex differentiation and characteristics in fetal and adult life. Any changes in the DNA or gene expression levels of LHCGR are associated with a variety of phenotypic as well as clinical symptoms and pathologies.

Human LHCGR gene is located on chromosome 2 and encodes 11 exons...


Luteinizing Hormone Testosterone Level Leydig Cell Azoospermia Serum Testosterone Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This study received no funding and the authors do not have any competing interests.

Conflict of interest

All authors contributed to design, acquisition, analysis, data intrepretation, and manuscript writing and declare no conflict of interest.


  1. 1.
    Jost A. Hormonal factors in the sex differentiation of the mammalian foetus. Philos Trans R Soc Lond B Biol Sci. 1970;259:119–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Sharpe RM. Pathways of endocrine disruption during male sexual differentiation and masculinization. Best Pract Res Clin Endocrinol Metab. 2006;20:91–110.PubMedCrossRefGoogle Scholar
  3. 3.
    Fowler PA, Bhattacharya S, Gromoll J, Monteiro A, O’Shaughnessy PJ. Maternal smoking and developmental changes in luteinizing hormone (LH) and the LH receptor in the fetal testis. J Clin Endocrinol Metab. 2009;94:4688–95.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Huhtaniemi I, Alevizaki M. Gonadotrophin resistance. Best Pract Res Clin Endocrinol Metab. 2006;20:561–76.PubMedCrossRefGoogle Scholar
  5. 5.
    Josso N, Picard JY, Tran D. The anti-mullerian hormone. Birth Defects Orig Artic Ser. 1977;13:59–84.PubMedGoogle Scholar
  6. 6.
    Siiteri PK, Wilson JD. Testosterone formation and metabolism during male sexual differentiation in the human embryo. J Clin Endocrinol Metab. 1974;38:113–25.PubMedCrossRefGoogle Scholar
  7. 7.
    Ascoli M, Fanelli F, Segaloff DL. The lutropin/choriogonadotropin receptor, a 2002 perspective. Endocrine reviews. 2002;23:141–74.PubMedCrossRefGoogle Scholar
  8. 8.
    Martens JW, Verhoef-Post M, Abelin N, Ezabella M, Toledo SP, Brunner HG, et al. A homozygous mutation in the luteinizing hormone receptor causes partial Leydig cell hypoplasia: correlation between receptor activity and phenotype. Mol Endocrinol. 1998;12:775–84.PubMedCrossRefGoogle Scholar
  9. 9.
    Bentov Y, Kenigsberg S, Casper RF. A novel luteinizing hormone/chorionic gonadotropin receptor mutation associated with amenorrhea, low oocyte yield, and recurrent pregnancy loss. Fertil Steril. 2012;97:1165–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Latronico AC, Anasti J, Arnhold IJ, Rapaport R, Mendonca BB, Bloise W, et al. Brief report: testicular and ovarian resistance to luteinizing hormone caused by inactivating mutations of the luteinizing hormone-receptor gene. N Engl J Med. 1996;334:507–12.PubMedCrossRefGoogle Scholar
  11. 11.
    Latronico AC, Chai Y, Arnhold IJ, Liu X, Mendonca BB, Segaloff DL. A homozygous microdeletion in helix 7 of the luteinizing hormone receptor associated with familial testicular and ovarian resistance is due to both decreased cell surface expression and impaired effector activation by the cell surface receptor. Mol Endocrinol. 1998;12:442–50.PubMedCrossRefGoogle Scholar
  12. 12.
    Stavrou SS, Zhu YS, Cai LQ, Katz MD, Herrera C, Defillo-Ricart M, et al. A novel mutation of the human luteinizing hormone receptor in 46XY and 46XX sisters. J Clin Endocrinol Metab. 1998;83:2091–8.PubMedGoogle Scholar
  13. 13.
    Toledo SP, Brunner HG, Kraaij R, Post M, Dahia PL, Hayashida CY, et al. An inactivating mutation of the luteinizing hormone receptor causes amenorrhea in a 46, XX female. J Clin Endocrinol Metab. 1996;81:3850–4.PubMedGoogle Scholar
  14. 14.
    Kremer H, Kraaij R, Toledo SP, Post M, Fridman JB, Hayashida CY, et al. Male pseudohermaphroditism due to a homozygous missense mutation of the luteinizing hormone receptor gene. Nat Genet. 1995;9:160–4.PubMedCrossRefGoogle Scholar
  15. 15.
    Laue L, Wu SM, Kudo M, Hsueh AJ, Cutler Jr GB, Griffin JE, et al. A nonsense mutation of the human luteinizing hormone receptor gene in Leydig cell hypoplasia. Hum Mol Genet. 1995;4:1429–33.PubMedCrossRefGoogle Scholar
  16. 16.
    Laue LL, Wu SM, Kudo M, Bourdony CJ, Cutler Jr GB, Hsueh AJ, et al. Compound heterozygous mutations of the luteinizing hormone receptor gene in Leydig cell hypoplasia. Mol Endocrinol. 1996;10:987–97.PubMedGoogle Scholar
  17. 17.
    Nieschlag E, Behre HM, Nieschlag S. Male Reproductive Health and Dysfunction 2010.Google Scholar
  18. 18.
    Hussein A, Ozgok Y, Ross L, Rao P, Niederberger C. Optimization of spermatogenesis-regulating hormones in patients with non-obstructive azoospermia and its impact on sperm retrieval: a multicentre study. BJU international. 2013;111:E110–4.PubMedCrossRefGoogle Scholar
  19. 19.
    Raman JD, Schlegel PN. Aromatase inhibitors for male infertility. J Urol. 2002;167:624–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Reifsnyder JE, Ramasamy R, Husseini J, Schlegel PN. Role of optimizing testosterone before microdissection testicular sperm extraction in men with nonobstructive azoospermia. Journal of Urology. 2012;188:532–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Shinjo E, Shiraishi K, Matsuyama H. The effect of human chorionic gonadotropin-based hormonal therapy on intratesticular testosterone levels and spermatogonial DNA synthesis in men with non-obstructive azoospermia. Andrology. 2013;1:929–35.PubMedCrossRefGoogle Scholar
  22. 22.
    Choi J, Smitz J. Luteinizing hormone and human chorionic gonadotropin: origins of difference. Mol Cell Endocrinol. 2014;383:203–13.PubMedCrossRefGoogle Scholar
  23. 23.
    Gromoll J, Eiholzer U, Nieschlag E, Simoni M. Male hypogonadism caused by homozygous deletion of exon 10 of the luteinizing hormone (LH) receptor: differential action of human chorionic gonadotropin and LH. J Clin Endocrinol Metab. 2000;85:2281–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Han B, Wang ZQ, Xue LQ, Ma JH, Liu W, Liu BL et al. Functional study of an aberrant splicing variant of the human luteinizing hormone (LH) receptor. Mol Hum Reprod;18:129-35.Google Scholar
  25. 25.
    Qiao J, Han B, Liu BL, Chen X, Ru Y, Cheng KX, et al. A splice site mutation combined with a novel missense mutation of LHCGR cause male pseudohermaphroditism. Hum Mutat. 2009;30:E855–65.PubMedCrossRefGoogle Scholar
  26. 26.
    Suganuma N, Furui K, Furuhashi M, Asada Y, Kikkawa F, Tomoda Y. Screening of the mutations in luteinizing hormone beta-subunit in patients with menstrual disorders. Fertil Steril. 1995;63:989–95.PubMedGoogle Scholar
  27. 27.
    Segaloff DL. Diseases associated with mutations of the human lutropin receptor. Progress in molecular biology and translational science. 2009;89:97–114.PubMedCrossRefGoogle Scholar
  28. 28.
    Piersma D, Verhoef-Post M, Look MP, Uitterlinden AG, Pols HA, Berns EM, et al. Polymorphic variations in exon 10 of the luteinizing hormone receptor: functional consequences and associations with breast cancer. Mol Cell Endocrinol. 2007;276:63–70.PubMedCrossRefGoogle Scholar
  29. 29.
    Kristiansen W, Aschim EL, Andersen JM, Witczak O, Fossa SD, Haugen TB. Variations in testosterone pathway genes and susceptibility to testicular cancer in Norwegian men. Int J Androl. 2012;35:819–27.PubMedCrossRefGoogle Scholar
  30. 30.
    Valkenburg O, Uitterlinden AG, Piersma D, Hofman A, Themmen AP, de Jong FH, et al. Genetic polymorphisms of GnRH and gonadotrophic hormone receptors affect the phenotype of polycystic ovary syndrome. Hum Reprod. 2009;24:2014–22.PubMedCrossRefGoogle Scholar
  31. 31.
    Mongan NP, Hughes IA, Lim HN. Evidence that luteinising hormone receptor polymorphisms may contribute to male undermasculinisation. Eur J Endocrinol. 2002;147:103–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Simoni M, Tuttelmann F, Michel C, Bockenfeld Y, Nieschlag E, Gromoll J. Polymorphisms of the luteinizing hormone/chorionic gonadotropin receptor gene: association with maldescended testes and male infertility. Pharmacogenet Genomics. 2008;18:193–200.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • M. E. Bakircioglu
    • 1
  • P. Tulay
    • 1
  • N. Findikli
    • 1
  • B. Erzik
    • 1
  • M. Gultomruk
    • 1
  • M. Bahceci
    • 1
  1. 1.Bahceci Assisted Reproductive Technology CentreKosuyolu CaddesiKadikoyTurkey

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