PMID- 22984182
OWN - NLM
STAT- MEDLINE
DCOM- 20121231
LR  - 20220321
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 109
IP  - 42
DP  - 2012 Oct 16
TI  - Testis tissue explantation cures spermatogenic failure in c-Kit ligand mutant 
      mice.
PG  - 16934-8
LID - 10.1073/pnas.1211845109 [doi]
AB  - 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.
FAU - Sato, Takuya
AU  - Sato T
AD  - Department of Urology, Yokohama City University Graduate School of Medicine, 
      Yokohama 236-0004, Japan.
FAU - Yokonishi, Tetsuhiro
AU  - Yokonishi T
FAU - Komeya, Mitsuru
AU  - Komeya M
FAU - Katagiri, Kumiko
AU  - Katagiri K
FAU - Kubota, Yoshinobu
AU  - Kubota Y
FAU - Matoba, Shogo
AU  - Matoba S
FAU - Ogonuki, Narumi
AU  - Ogonuki N
FAU - Ogura, Atsuo
AU  - Ogura A
FAU - Yoshida, Shosei
AU  - Yoshida S
FAU - Ogawa, Takehiko
AU  - Ogawa T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120910
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (KITL2 protein, mouse)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Stem Cell Factor)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
SB  - IM
CIN - Nat Rev Urol. 2012 Nov;9(11):604. PMID: 23027066
CIN - Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):16762-3. PMID: 23047695
MH  - Animals
MH  - Cell Culture Techniques
MH  - Infertility, Male/genetics/*therapy
MH  - Macrophage Colony-Stimulating Factor/metabolism
MH  - Male
MH  - Mice
MH  - Recombinant Proteins/*genetics/pharmacology
MH  - Sertoli Cells/metabolism
MH  - Spermatogenesis/drug effects/*genetics
MH  - Spermatogonia/drug effects/physiology
MH  - Stem Cell Factor/*genetics/metabolism/pharmacology
MH  - Testis/*cytology/physiology
PMC - PMC3479468
COIS- The authors declare no conflict of interest.
EDAT- 2012/09/18 06:00
MHDA- 2013/01/01 06:00
PMCR- 2013/04/16
CRDT- 2012/09/18 06:00
PHST- 2012/09/18 06:00 [entrez]
PHST- 2012/09/18 06:00 [pubmed]
PHST- 2013/01/01 06:00 [medline]
PHST- 2013/04/16 00:00 [pmc-release]
AID - 1211845109 [pii]
AID - 201211845 [pii]
AID - 10.1073/pnas.1211845109 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):16934-8. doi: 
      10.1073/pnas.1211845109. Epub 2012 Sep 10.