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1 January 2002 Restoration of Spermatogenesis and Fertility in Azoospermic Mutant Mice by Suppression and Reelevation of Testosterone Followed by Intracytoplasmic Sperm Injection
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Abstract

Advances in assisted reproduction techniques such as in vitro fertilization and intracytoplasmic sperm injection have made paternity possible for many patients with male infertility. However, at least some sperm or spermatids are required for these techniques to be successful, and patients incapable of producing spermatids cannot be helped. Male mice homozygous for the mutant juvenile spermatogonial depletion (jsd) gene show spermatogonial arrest and an elevated intratesticular testosterone level like many other experimental infertility models such as those with iradiation- or chemotherapy-induced testicular damage. In this category of infertile males, suppression of the testosterone level induces spermatogonial differentiation to the stage of spermatocytes but no further. In the present study with jsd mutant mice, we induced spermatogenesis first to spermatocytes and then to elongated spermatids by suppression of testosterone levels with a GnRH antagonist, Nal-Glu, at a dose of 2500 μg kg−1 day−1 for 4 wk and then withdrawal of Nal-Glu. Spermatids were seen in the cross-sections of seminiferous tubules in all mice treated by administration and subsequent withdrawal of Nal-Glu. Four weeks after withdrawal of Nal-Glu, some of the germ cells differentiated into elongated spermatids. Supplementation with testosterone and Nal-Glu after 4 wk of treatment with Nal-Glu alone also induced spermatogenesis similar to the induction by withdrawal of Nal-Glu. Thus, we ascribe the restoration of the differentiation of spermatocytes to spermatids to reelevation of the testosterone level. Furthermore, we successfully rescued male sterility in jsd mice by subsequent intracytoplasmic sperm injection using the elongated spermatids induced by the programmed hormone therapy.

Akira Tohda, Tsuyoshi Okuno, Kiyomi Matsumiya, Masaru Okabe, Hidefumi Kishikawa, Kayoko Dohmae, Akihiko Okuyama, and Yoshitake Nishimune "Restoration of Spermatogenesis and Fertility in Azoospermic Mutant Mice by Suppression and Reelevation of Testosterone Followed by Intracytoplasmic Sperm Injection," Biology of Reproduction 66(1), 85-90, (1 January 2002). https://doi.org/10.1095/biolreprod66.1.85
Published: 1 January 2002
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