Impact of genetic engineering on the understanding of spermatogenesis

Escalier, Denise

doi:10.1093/humupd/7.2.191

Cited by 91 publications

(76 citation statements)

References 216 publications

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“…We are currently investigating the potential binding partner(s) of CIB1 in order to further determine the mechanism by which CIB1 regulates spermatogenesis. Our findings here suggest that CIB1 null mice may provide a useful research model for understanding human male idiopathic infertility and thus fertility drug targets (4,6).…”

Section: Discussionmentioning

confidence: 71%

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CIB1 Is Essential for Mouse Spermatogenesis

Yuan¹,

Leisner²,

McFadden³

et al. 2006

Molecular and Cellular Biology

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CIB1 is a 22-kDa calcium binding, regulatory protein with ϳ50% homology to calmodulin and calcineurin B. CIB1 is widely expressed and binds to a number of effectors, such as integrin ␣IIb, PAK1, and polo-like kinases, in different tissues. However, the in vivo functions of CIB1 are not well understood. To elucidate the function of CIB1 in whole animals, we used homologous recombination in embryonic stem cells to generate Cib1 ؊/؊ mice. Although Cib1 ؊/؊ mice grow normally, the males are sterile due to disruption of the haploid phase of spermatogenesis. This is associated with reduced testis size and numbers of germ cells in seminiferous tubules, increased germ cell apoptosis, and the loss of elongated spermatids and sperm. Cib1؊/؊ testes also show increased mRNA and protein expression of the cell cycle regulator Cdc2/Cdk1. In addition, mouse embryonic fibroblasts (MEFs) derived from Cib1 ؊/؊ mice exhibit a much slower growth rate compared to Cib1 ؉/؉ MEFs, suggesting that CIB1 regulates the cell cycle, differentiation of spermatogenic germ cells, and/or differentiation of supporting Sertoli cells.

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Section: Discussionmentioning

confidence: 71%

“…Spermatogenesis is the long, complex process by which germ cells are produced through successive periods of regulated cell proliferation, meiosis, and haploid differentiation (6,19). During spermatogenesis in the mammalian testis, stem cells proliferate to produce spermatogonia, which differentiate into primary spermatocytes.…”

mentioning

confidence: 99%

CIB1 Is Essential for Mouse Spermatogenesis

Yuan¹,

Leisner²,

McFadden³

et al. 2006

Molecular and Cellular Biology

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“…Nonetheless, our successful production of offspring from an infertile male mouse suggests a promising possibility for the gene therapy approach in the treatment of male infertility. A number of infertile mutants in mice are caused by genetic defects in Sertoli cell function, which strongly suggest that some cases of human male infertility may be associated with Sertoli cell dysfunction (49), and improvements in the gene transfer technology will certainly increase mature spermatozoa production. Extensive studies on sequencing spermatogenesis genes and their site of expression as well as how to safely correct genes are clearly required for the possibility of gene therapy for male infertility at this stage of research.…”

Section: Discussionmentioning

confidence: 99%

Adenovirus-mediated gene delivery and in vitro microinsemination produce offspring from infertile male mice

Kanatsu-Shinohara

Ogura²,

Ikegawa³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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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 Steel͞Steel dickie (Sl͞Sl 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.

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“…Mouse studies have shown that 4100 genes are involved in spermatogenesis. 3 When knockout mice for these genes were made, defects were often pleiotropic and thus not restricted to an impaired spermatogenesis.…”

Section: Introductionmentioning

confidence: 99%

Possible role of USP26 in patients with severely impaired spermatogenesis

et al. 2004

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The ubiquitin-specific protease 26 (USP26) gene is an X-linked gene specifically expressed in testis tissue. This gene is therefore a potential infertility gene. In order to analyse its possible involvement in spermatogenesis and infertility, 42 patients with Sertoli cell-only syndrome were analysed for mutations in this gene. We found four patients with exactly the same three changes of the nucleotide and therefore also amino acid sequence. These patients showed 370-371insACA, 494T4C and 1423C4T causing T123-124ins, L165S and H475Y, respectively. These changes were not found in 10 control samples. Furthermore, two polymorphisms were observed which do not alter the amino-acid sequence. A restriction analysis that can make a distinction between a T and a C, at position 494, was set up in order to examine more patient and control samples. Another 69 patients with Sertoli cell-only syndrome, 32 patients with maturation arrest and 142 control samples were analysed using this method. None of the control samples or patients with maturation arrest featured the change at position 494. However, four more patients with Sertoli cell-only syndrome were identified with the three alterations. The frequency of alterations in this group is therefore 7.2% (8/111). One of the patients had a deletion of the long arm of the Y chromosome, while another patient had a varicocoele. These results indicate that these alterations might be involved in male infertility or might increase the risk of male infertility.

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Impact of genetic engineering on the understanding of spermatogenesis

Cited by 91 publications

References 216 publications

CIB1 Is Essential for Mouse Spermatogenesis

CIB1 Is Essential for Mouse Spermatogenesis

Adenovirus-mediated gene delivery and in vitro microinsemination produce offspring from infertile male mice

Possible role of USP26 in patients with severely impaired spermatogenesis

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