title: Testis tissue explantation cures spermatogenic failure in c-Kit ligand mutant mice.
abstract: Male infertility is most commonly caused by spermatogenic defects or insufficiencies, the majority of which are as yet cureless. Recently, we succeeded in cultivating mouse testicular tissues for producing fertile sperm from spermatogonial stem cells. Here, we show that one of the most severe types of spermatogenic defect mutant can be treated by the culture method without any genetic manipulations. The Sl/Sl(d) mouse is used as a model of such male infertility. The testis of the Sl/Sl(d) mouse has only primitive spermatogonia as germ cells, lacking any sign of spermatogenesis owing to mutations of the c-kit ligand (KITL) gene that cause the loss of membrane-bound-type KITL from the surface of Sertoli cells. To compensate for the deficit, we cultured testis tissues of Sl/Sl(d) mice with a medium containing recombinant KITL and found that it induced the differentiation of spermatogonia up to the end of meiosis. We further discovered that colony stimulating factor-1 (CSF-1) enhances the effect of KITL and promotes spermatogenesis up to the production of sperm. Microinsemination of haploid cells resulted in delivery of healthy offspring. This study demonstrated that spermatogenic impairments can be treated in vitro with the supplementation of certain factors or substances that are insufficient in the original testes.
authors.affiliation: Department of Urology,  Yokohama City University Graduate School of Medicine, Yokohama 236-0004,  Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Sato
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Yokonishi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Komeya
authors.forename: Kumiko
authors.initials: K
authors.lastname: Katagiri
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kubota
authors.forename: Shogo
authors.initials: S
authors.lastname: Matoba
authors.forename: Narumi
authors.initials: N
authors.lastname: Ogonuki
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ogura
authors.forename: Shosei
authors.initials: S
authors.lastname: Yoshida
authors.forename: Takehiko
authors.initials: T
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D007248:Infertility, Male / Q000235:genetics / Q000628:therapy*; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008297:Male; D051379:Mice; D011994:Recombinant Proteins / Q000235:genetics* / Q000494:pharmacology; D012708:Sertoli Cells / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects / Q000235:genetics*; D013093:Spermatogonia / Q000187:drug effects / Q000502:physiology; D019089:Stem Cell Factor / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D013737:Testis / Q000166:cytology* / Q000502:physiology
chemical_list: C527451:KITL2 protein, mouse; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016173:Macrophage Colony-Stimulating Factor