Stimulation of spermatogonial differentiation in juvenile spermatogonial depletion (jsd) mutant mice by gonadotropin-releasing hormone antagonist treatment.
Male juvenile spermatogonial depletion (jsd) mutant mice are sterile because of spermatogenic failure and so may provide a model for genetically caused human male infertility. To test the effects of testosterone suppression therapy on spermatogenesis in jsd/jsd mice, we treated them with Nal-Glu, a GnRH antagonist. Treatment with Nal-Glu at 2500 microg/kg/day was started at 5.5 or 8 weeks of age and continued for 4 or 8 weeks. Differentiation of spermatogonia was evaluated by the percentage of tubules containing two or more spermatocytes (% of differentiating tubules). Nal-Glu treatment caused a marked decrease in the weights of the testes and seminal vesicles and intratesticular testosterone concentrations. However, in contrast to a value of 1.3% in untreated jsd/jsd mice, the mean % of differentiating tubules was 59.9% and 25.1% in treatment groups started at 5.5 and 8 weeks of age, respectively. We propose that spermatogonial differentiation in jsd/jsd mutant mice is sensitive to the high intratesticular levels of testosterone and can only proceed when testosterone production is suppressed.
Matsumiya
K
K
Department of Urology, Osaka University Medical School, Suita, Japan.
Meistrich
M L
ML
Shetty
G
G
Dohmae
K
K
Tohda
A
A
Okuyama
A
A
Nishimune
Y
Y
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006727:Hormone Antagonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000502:physiology*; D009929:Organ Size / Q000187:drug effects; D012669:Seminal Vesicles / Q000033:anatomy & histology; D012671:Seminiferous Tubules / Q000187:drug effects; D013093:Spermatogonia / Q000166:cytology* / Q000502:physiology*; D013737:Testis / Q000033:anatomy & histology / Q000378:metabolism; D013739:Testosterone / Q000037:antagonists & inhibitors
C102118:2-naphthylalanyl-glutamic acid; D004151:Dipeptides; D006727:Hormone Antagonists; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone