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BOR - Papers in Press, published online ahead of print February 5, 2003.
Biol Reprod 2003, 10.1095/biolreprod.102.013276
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BIOLOGY OF REPRODUCTION 68, 2304–2313 (2003)
DOI: 10.1095/biolreprod.102.013276
© 2003 by the Society for the Study of Reproduction, Inc.


Testis

Increment of Murine Spermatogonial Cell Number by Gonadotropin-Releasing Hormone Analogue Is Independent of Stem Cell Factor c-kit Signal1

Masako Ohmura3, Takehiko Ogawa2,4, Michio Ono3, Mari Dezawa3, Masahiko Hosaka4, Yoshinobu Kubota4, and Hajime Sawada3

Department of Anatomy3 Urology,4 Yokohama City University School of Medicine, Yokohama 236-0004, Japan

Recent studies have demonstrated that GnRH-analogues can stimulate regeneration of spermatogenesis of rats when administered after testicular damages. Although the mechanism of this phenomenon has not been elucidated yet, stem cell factor (SCF) produced by Sertoli cells was proposed to mediate the effects of GnRH-analogues on spermatogonial proliferation and/or survival. In the present study, we quantitatively evaluated the proliferation of spermatogonia and addressed whether SCF mediates the effect of GnRH-analogue on spermatogonial proliferation, using a novel approach combining spermatogonial transplantation and laser confocal microscopic observation. In the first experiment, using wild-type mice as recipients for spermatogonial transplantation, the number of donor spermatogonia per 100 Sertoli cells in each spermatogenic colony was significantly higher in the experimental group of mice treated with leuprorelin, a GnRH-agonist, than that of the control group at 4 and 5 wk after transplantation. In the second experiment, Steel/Steeldickie (Sl/Sld) mutant mice, which lack expression of membrane bound form SCF, were used as recipients. As seen in the first experiment, the number of undifferentiated spermatogonia was significantly higher in leuprorelin-treated than in the control group. Since undifferentiated spermatogonia do not express the receptor of SCF, the present study clearly demonstrates that neither membrane-bound nor secreted forms of SCF are involved in the mechanism of GnRH-analogue's effect on spermatogonial proliferation and/or survival.

1 This work was supported by Grant-in-Aids for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan (13671663 to T.O. and 12370025 to H.S.), and a Grant-in-Aid from Yokohama Foundation for Advancement of Medical Science (to T.O.).

2 Correspondence: Takehiko Ogawa, Department of Urology, Yokohama City University School of Medicine, Fukuura 3-9, Kanazawa-ku, Yokohama 236-0004, Japan. Fax: 81 45 786 5775; ogawa{at}med.yokohama-cu.ac.jp




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