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 L. Hess, Marvin L. Meistrich

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    29 Scopus citations

    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
    DOIs
    StatePublished - 2005

    Keywords

    • Macaque
    • Spermatogenesis
    • Testis

    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism
    • Reproductive Medicine
    • Endocrinology
    • Urology

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    Boekelheide, K., Schoenfeld, H. A., Hall, S. J., Weng, C. C., Shetty, G., Leith, J., Harper, J., Sigman, M., Hess, D. L., & 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. https://doi.org/10.1002/j.1939-4640.2005.tb01089.x