Document Detail


Adenovirus-mediated gene delivery and in vitro microinsemination produce offspring from infertile male mice.
MedLine Citation:
PMID:  11818536     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Sertoli cells play a pivotal role in spermatogenesis through their interactions with germ cells. To set up a strategy for treating male infertility caused by Sertoli cell dysfunction, we developed a Sertoli cell gene transfer system by using an adenovirus vector, which maintained long-term transgene expression in the testes of infertile mice. Introduction of an adenovirus carrying the mouse Steel (Sl) gene into Sertoli cells restored partial spermatogenesis in infertile Steel/Steel(dickie) (Sl/Sl(d)) mutant mouse testes. Although these males remained infertile, round spermatids and spermatozoa from the testes produced normal fertile offspring after intracytoplasmic injection into oocytes. None of the offspring showed evidence of germ line transmission of adenoviral DNA. Thus, we demonstrate a successful treatment for infertility by using a gene therapy vector. Therefore, adenovirus-mediated gene delivery into Sertoli cells not only provides an efficient and convenient means for studying germ cell-Sertoli cell interactions through manipulation of the germ cell microenvironment in vivo, but also is a useful method to treat male infertility resulting from a Sertoli cell defect.
Authors:
Mito Kanatsu-Shinohara; Atsuo Ogura; Masaya Ikegawa; Kimiko Inoue; Narumi Ogonuki; Kei Tashiro; Shinya Toyokuni; Tasuku Honjo; Takashi Shinohara
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2002-01-29
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  99     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-02-06     Completed Date:  2002-03-07     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1383-8     Citation Subset:  IM    
Affiliation:
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics*
Animals
Chromatin / ultrastructure
Crosses, Genetic
Gene Transfer Techniques*
Genetic Vectors*
Infertility, Male / genetics*
Insemination / genetics
Male
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Microinjections
Spermatids / cytology
Spermatogenesis
Spermatozoa / cytology
beta-Galactosidase / genetics
Chemical
Reg. No./Substance:
0/Chromatin; EC 3.2.1.23/beta-Galactosidase
Comments/Corrections

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