RRC ID 18541
Author Sato T, Yokonishi T, Komeya M, Katagiri K, Kubota Y, Matoba S, Ogonuki N, Ogura A, Yoshida S, Ogawa T.
Title Testis tissue explantation cures spermatogenic failure in c-Kit ligand mutant mice.
Journal Proc Natl Acad Sci U S A
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.
Volume 109(42)
Pages 16934-8
Published 2012-10-16
DOI 10.1073/pnas.1211845109
PII 1211845109
PMID 22984182
PMC PMC3479468
MeSH Animals Cell Culture Techniques Infertility, Male / genetics Infertility, Male / therapy* Macrophage Colony-Stimulating Factor / metabolism Male Mice Recombinant Proteins / genetics* Recombinant Proteins / pharmacology Sertoli Cells / metabolism Spermatogenesis / drug effects Spermatogenesis / genetics* Spermatogonia / drug effects Spermatogonia / physiology Stem Cell Factor / genetics* Stem Cell Factor / metabolism Stem Cell Factor / pharmacology Testis / cytology* Testis / physiology
IF 9.412
Times Cited 38
Mice RBRC00445