Purpose: In boys with cryptorchidism older than 2 years a testicular biopsy at time of orchiopexy shows lack of germ cells in 10–40% of the cases. The number of spermatogonia per tubule is prognostic for subsequent fertility potential. A biopsy without germ cells is associated with 33–100% risk of infertility. In order to increase the number of germ cells, and thereby the fertility potential, additional hormonal therapy has been attempted before surgery. In a study, small doses of the gonadotropin-releasing hormone analogue buserelin before orchiopexy caused higher values. Others have found that hormonal treatment with human chorionic gonadotropin or gonadotropin releasing hormone analogue may harm the germ cells in cryptorchidism. The aim of the study is to demonstrate that additional hormonal therapy with erythropoietin has a positive effect on the number of germ cells. Materials and Methods: Erythropoietin (Eprex) 100 IU/kg were administered subcutaneously weekly for 3 months prior to surgery in two cryptorchid boys, 6 months old and 1 year 9 months old, respectively, with renal function impairment. Results: The number of spermatogonia per tubular cross-section in testicular biopsies was unusually high in both erythropoietin- treated cryptorchid cases compared to the control material of biopsies from the undescended testes of 698 cryptorchid patients and compared to the normal values. Conclusion: There are several hypothetic mechanisms that can explain the elevated number of spermatogonia seen in our erythropoietin treated cryptorchid patients. Erythropoietin may have a positive effect on germ cell proliferation in cryptorchidism.

Keywords:
Cryptorchidism, Spermatogonia, Erythropoietin
1.
Cortes D: Cryptorchidism – aspects of pathogenesis, histology and treatment. Scand J Urol Nephrol 1998;32(suppl 196):1998.
2.
Hadziselimovic F, Hecker E, Herzog B: The value of testicular biopsy in cryptorchidism. Urol Res 1984;12:171.
3.
Cortes D, Thorup JM, Beck BL: Quantitative histology of germ cells in undescended testes of human fetuses, neonates and infants. J Urol 1995;154:1188.
4.
Bica DTG, Hadziselimovic F: Buserelin treatment of cryptorchidism: A randomized double-blind, placebo-controlled study. J Urol 1992;148:617.
5.
Cortes D, Thorup J, Visfeldt J: Hormonal treatment may harm germ cells in 1- to 3-year old boys with cryptorchidism. J Urol 2000;163:1290.
6.
Visfeldt J, Cortes D, Thorup JM, Byskov AG: Anti-MIC2 as a tool in examination of testicular biopsies. APMIS 1999;107:631.
7.
Cortes D: Histological versus stereological methods applied at spermatogonia during normal human development. Scand J Urol Nephrol 1990;24:11.
8.
Cortes D, Thorup J, Visfeldt J: Cryptorchidism: Aspects of fertility and neoplasms. Horm Res 2001;55:21–27.
9.
Foresta C, Mioni R, Bardon P, Gottardello F, Nogara A, Rossato M: Erythropoietin and testicular steroidogenesis: The role of second messengers. Eur J Endocrinol 1995;132:103.
10.
Tan CC, Eckardt KU, Firth JD, Ratcliffe PJ: Feedback modulation of renal and hepatic erythropoietin mRNA in response to graded anemia and hypoxia. Am J Physiol 1992;263:F474.
11.
Sharpe RM: Regulation of spermatogenesis; in Knobil E, Neill JD (eds): The Physiology of Reproduction, ed 2. New York, Raven Press, 1994.
12.
Foresta C, Mioni R, Bordon P, Miotto D, Montini G, Varotto A: Erythropoietin stimulates testosterone production in man. J Clin Endocrinol Metab 1994;78:753.
13.
D’Andrea AD, Fasman G, Lodish HF: Erythropoietin receptor and interleukin-2 receptor beta-chain: A new receptor family. Cell 1989;58:1023.
14.
Burke BA, Lindgren B, Wick M, Holley K, Manivel C: Testicular germ cell loss in children with renal failure. Pediatr Pathol 1989;9:433.
15.
Renshaw AA: Testicular calcifications: Incidence, histology and proposed pathological criteria for testicular microlithiasis. J Urol 1998;160:1625.
16.
Marder HK, Srivastave LS, Burnstein S: Hypergonadotropism in peripubertal boys with chronic renal failure. Pediatrics 1983;72:384.
17.
Kokot F, Wiecek A, Schmidt-Gayk H, Marcinkowski W, Gilge U, Heidland A, Rudka R, Trembecki J: Function of endocrine organs in hemodialyzed patients of long-term erythropoietin therapy. Artif Organs 1995;19:428.
18.
Fox RA, Sigman M, Boekelheide K. Transmembrane versus soluble stem cell factor expression in human testis. J Androl 2000;21:579.
19.
Lin Y, Benchimol S: Cytokines inhibit p53-mediated apoptosis but not p53-mediated G1 arrest. Mol Cell Biol 1995;15:6045.
20.
Socher SA, Yin Y, Dewolf WC, Morgentaler A: Temperature-mediated germ cell loss in the testis is associated with altered expression of the cell-cycle regulator p53. J Urol 1997;157:1986.
© 2001 S. Karger AG, Basel
2001
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