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Hum. Reprod. Advance Access originally published online on January 5, 2006
Human Reproduction 2006 21(4):1033-1040; doi:10.1093/humrep/dei444
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Testis morphology in patients with idiopathic hypogonadotropic hypogonadism

Pananghat A. Kumar1,*, Nelly Pitteloud2,*, Peter A.M. Andrews1, Andrew Dwyer2, Frances Hayes2, William F. Crowley, Jr2 and Martin Dym1,3

1 Department of Cell Biology, Georgetown University Medical Center, Washington DC USA and 2 Reproductive Endocrine Unit, Massachusetts General Hospital and the Harvard Reproductive Endocrine Sciences Center, Boston MA USA

3 To whom correspondence is to be addressed at: Department of Cell Biology, Georgetown University Medical Center, 3900 Reservoir Road NW, Washington DC 20057 USA. E-mail: dymm{at}georgetown.edu

BACKGROUND: Adult patients with idiopathic hypogonadotropic hypogonadism (IHH) typically present with absent puberty and therefore have prepubertal testes. IHH is recognized as one of the few curable causes of male infertility and is often effectively treated with either gonadotropins or pulsatile GnRH therapy. The objective of this study was to determine the structure of the testis prior to initiation of treatment. METHODS AND RESULTS: Eight adult IHH patients with prepubertal testes (<4 ml), with no previous gonadotropin therapy and with no history of cryptorchidism underwent open bilateral testicular biopsy prior to the initiation of hormonal treatment. The testes of all patients showed seminiferous cords separated by interstitium composed of blood vessels, connective tissue cells and collagen fibres but typical adult Leydig cells were absent. The cords contained only Sertoli cells and early type A spermatogonia. The spermatogonia mostly resided in the centre of the cords and were often large, typical of gonocytes. Sertoli cells appeared immature with ovoid nuclei devoid of infoldings and cytoplasm that lacked polarity. Tight junctional complexes commonly found connecting adult Sertoli cells were lacking. CONCLUSIONS: These results demonstrate that the immature testes from patients with the severe form of IHH possess early spermatogonia that could possibly reinitiate spermatogenesis with appropriate hormone stimulation. Therefore, the immature testis of this IHH subset resembles those of prepubertal boys and may provide important biologic and genetic insights into testicular development.

Key words: hormonal therapy/idiopathic hypogonadotropic hypogonadism/Sertoli cells/spermatogonia/testis

* These authors are equal first authors of the article


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