Gonadotropin-releasing hormone antagonist (cetrorelix) therapy fails to protect nonhuman primates (Macaca arctoides) from radiation-induced spermatogenic failure

Kim Boekelheide, Heidi A. Schoenfeld, Susan J. Hall, Connie C. Weng, Gunapala Shetty, John Leith, James Harper, Mark Sigman, David Hess, Marvin L. Meistrich

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Treatment of men of reproductive age with radiation or alkylating agents often produces prolonged azoospermia. We previously demonstrated that suppression of testosterone (T) with gonadotropin-releasing hormone (GnRH) analogs restored spermatogenesis following atrophy induced by radiation or chemotherapy in rats. This study tested whether GnRH antagonist therapy could reverse radiation-induced testicular injury in primates with a similar protocol. Adult male stump-tailed macaques were given either 6.7 Gy radiation to the testis alone, 6.7 Gy radiation combined with GnRH-antagonist treatment starting on the day of exposure, or daily injections of the GnRH antagonist Cetrorelix for 3 months alone and were monitored for 18 months. Cetrorelix alone produced a 20-40-week fully reversible suppression of serum T, but although spermatogenic recovery was incomplete, 40%-90% of tubules contained differentiating germ cells. Following radiation alone, testis volumes were reduced to approximately 28% and sperm counts to less than 1% of pretreatment values. A biopsy at 18 months after radiation showed that only 3.0% of seminiferous tubule cross sections had germ cells. In irradiated animals that received GnRH antagonist, testis volumes were reduced to 18% of pretreatment volume, and at 18 months, only 1.9% of seminiferous tubule cross sections contained germ cells. Inhibin B values were reduced to 10% and 3% of pretreatment levels in the radiation-only and the radiation plus GnRH antagonist groups, respectively. Species differences exist in the testicular response to radiation, GnRH antagonist therapy, or both, so that rescue protocols that were successful in rodents might network in primates.

Original languageEnglish (US)
Pages (from-to)222-234
Number of pages13
JournalJournal of Andrology
Volume26
Issue number2
StatePublished - Mar 2005
Externally publishedYes

Fingerprint

Hormone Antagonists
Macaca
Gonadotropin-Releasing Hormone
Primates
Radiation
Germ Cells
Testis
Radiation Dosage
Seminiferous Tubules
Therapeutics
Azoospermia
Sperm Count
cetrorelix
Alkylating Agents
Spermatogenesis
Atrophy
Testosterone
Rodentia
Biopsy
Drug Therapy

Keywords

  • Macaque
  • Spermatogenesis
  • Testis

ASJC Scopus subject areas

  • Endocrinology

Cite this

Boekelheide, K., Schoenfeld, H. A., Hall, S. J., Weng, C. C., Shetty, G., Leith, J., ... Meistrich, M. L. (2005). Gonadotropin-releasing hormone antagonist (cetrorelix) therapy fails to protect nonhuman primates (Macaca arctoides) from radiation-induced spermatogenic failure. Journal of Andrology, 26(2), 222-234.

Gonadotropin-releasing hormone antagonist (cetrorelix) therapy fails to protect nonhuman primates (Macaca arctoides) from radiation-induced spermatogenic failure. / Boekelheide, Kim; Schoenfeld, Heidi A.; Hall, Susan J.; Weng, Connie C.; Shetty, Gunapala; Leith, John; Harper, James; Sigman, Mark; Hess, David; Meistrich, Marvin L.

In: Journal of Andrology, Vol. 26, No. 2, 03.2005, p. 222-234.

Research output: Contribution to journalArticle

Boekelheide, K, Schoenfeld, HA, Hall, SJ, Weng, CC, Shetty, G, Leith, J, Harper, J, Sigman, M, Hess, D & Meistrich, ML 2005, 'Gonadotropin-releasing hormone antagonist (cetrorelix) therapy fails to protect nonhuman primates (Macaca arctoides) from radiation-induced spermatogenic failure', Journal of Andrology, vol. 26, no. 2, pp. 222-234.
Boekelheide, Kim ; Schoenfeld, Heidi A. ; Hall, Susan J. ; Weng, Connie C. ; Shetty, Gunapala ; Leith, John ; Harper, James ; Sigman, Mark ; Hess, David ; Meistrich, Marvin L. / Gonadotropin-releasing hormone antagonist (cetrorelix) therapy fails to protect nonhuman primates (Macaca arctoides) from radiation-induced spermatogenic failure. In: Journal of Andrology. 2005 ; Vol. 26, No. 2. pp. 222-234.
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abstract = "Treatment of men of reproductive age with radiation or alkylating agents often produces prolonged azoospermia. We previously demonstrated that suppression of testosterone (T) with gonadotropin-releasing hormone (GnRH) analogs restored spermatogenesis following atrophy induced by radiation or chemotherapy in rats. This study tested whether GnRH antagonist therapy could reverse radiation-induced testicular injury in primates with a similar protocol. Adult male stump-tailed macaques were given either 6.7 Gy radiation to the testis alone, 6.7 Gy radiation combined with GnRH-antagonist treatment starting on the day of exposure, or daily injections of the GnRH antagonist Cetrorelix for 3 months alone and were monitored for 18 months. Cetrorelix alone produced a 20-40-week fully reversible suppression of serum T, but although spermatogenic recovery was incomplete, 40{\%}-90{\%} of tubules contained differentiating germ cells. Following radiation alone, testis volumes were reduced to approximately 28{\%} and sperm counts to less than 1{\%} of pretreatment values. A biopsy at 18 months after radiation showed that only 3.0{\%} of seminiferous tubule cross sections had germ cells. In irradiated animals that received GnRH antagonist, testis volumes were reduced to 18{\%} of pretreatment volume, and at 18 months, only 1.9{\%} of seminiferous tubule cross sections contained germ cells. Inhibin B values were reduced to 10{\%} and 3{\%} of pretreatment levels in the radiation-only and the radiation plus GnRH antagonist groups, respectively. Species differences exist in the testicular response to radiation, GnRH antagonist therapy, or both, so that rescue protocols that were successful in rodents might network in primates.",
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