Production of the antiviral proteins 2′5′oligoadenylate synthetase, PKR and Mx in interstitial cells and spermatogonia

Melaine, Nathalie; Liénard, Marie-Odile; Guillaume, Elisabeth; Ruffault, Annick; Dejucq-Rainsford, Nathalie; Jégou, Bernard

doi:10.1016/s0165-0378(02)00061-x

Cited by 25 publications

(24 citation statements)

References 13 publications

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“…Overall, our data indicate that type I IFN signaling does not operate in germ cells from the pachytene stage of spermatocytes to postmeiotic spermatids. In contrast, we found that the population of early primary spermatocytes (before the pachytene stage) and spermatogonia expressed both subunits of the IFN receptor, which is consistent with our previous data showing responsiveness of rat premeiotic germ cells to IFN␣ (11) and the fact that several ISGs appeared to be induced in situ in premeiotic/early meiotic germ cells of 45-day-old Tg10 (Fig. 10).…”

Section: Discussionsupporting

confidence: 93%

Excess Type I Interferon Signaling in the Mouse Seminiferous Tubules Leads to Germ Cell Loss and Sterility

Satie

Mazaud-Guittot

Seif

et al. 2011

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 93%

Excess Type I Interferon Signaling in the Mouse Seminiferous Tubules Leads to Germ Cell Loss and Sterility

Satie

Mazaud-Guittot

Seif

et al. 2011

Journal of Biological Chemistry

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“…Previous data appear to support the notion that both oocytes and ES cells, unlike most of the somatic cell types, lack or are insensitive to the IFN response triggered by dsRNAs because introduction of dsRNAs into these cells do not activate the OASRNaseL pathway, which usually leads to the cell's demise (33)(34)(35). Given that the testis is an immune-privileged organ that has been shown to tolerate antigen introduction without eliciting immune responses (36,37) and to respond poorly to RNA virus stimulation (38,39), testicular cells, at least the developing male germ cells, may lack IFN response and thus can produce endo-siRNAs using naturally occurring long dsRNAs. Here, we show that the mouse testis, indeed, expresses numerous endo-siRNAs, which are mostly derived from trans-nat-dsRNAs and hairpin dsRNAs.…”

mentioning

confidence: 74%

Male germ cells express abundant endogenous siRNAs

Song

Hennig

et al. 2011

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

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In mammals, endogenous siRNAs (endo-siRNAs) have only been reported in murine oocytes and embryonic stem cells. Here, we show that murine spermatogenic cells express numerous endo-siRNAs, which are likely to be derived from naturally occurring doublestranded RNA (dsRNA) precursors. The biogenesis of these testicular endo-siRNAs is DROSHA independent, but DICER dependent. These male germ cell endo-siRNAs can potentially target hundreds of transcripts or thousands of DNA regions in the genome. Overall, our work has unveiled another hidden layer of regulation imposed by small noncoding RNAs during male germ cell development.RNA interference | spermatogenesis | testis | interferon response R NA interference (RNAi) is a highly conserved gene silencing mechanism by which double-stranded RNAs (dsRNAs) are processed into single-stranded RNAs (ssRNAs) followed by loading onto effector complexes to modulate gene expression (1, 2). Small interfering RNAs (siRNAs) represent one of several distinct classes of small noncoding RNAs identified so far. Previously, siRNAs mainly referred to small ssRNAs processed in the host cells from exogenous dsRNAs (e.g., hairpin dsRNAs, synthetic short dsRNAs, etc.), and these artificial siRNAs have been widely used to suppress target gene expression both in vitro and in vivo (3-5). Endogenous siRNAs (endo-siRNAs) were initially identified in yeasts, plants, and Caenorhabditis elegans (6-9), and biogenesis of endo-siRNAs in these organisms depends on the activity of RNAdependent RNA polymerase (RdRP), which catalyzes the replication of RNA from an RNA template (8-11). Double-stranded RNAs (dsRNAs) produced by RdRP are then cleaved by the RNase III DICER to generate single-stranded mature endo-siRNAs. By associating with Argonaute (AGO) proteins, siRNAs negatively regulate the expression of targeting genes at posttranscriptional levels by inducing mRNA degradation and/or translational suppression (10-12). Alternatively, these endo-siRNAs can function as guidance molecules to direct associated protein factors to target specific genomic regions by DNA cytosine methylation or promoting the formation of heterochromatin (13,14).Although RdRP has not been found in flies or mice, certain cell types of these two species appear to be able to generate endosiRNAs by processing the naturally occurring dsRNAs (15-23). These dsRNA precursors include hairpin-dsRNAs, trans-natural antisense transcript-derived dsRNAs (trans-nat-dsRNAs), and cisnatural antisense transcript-derived dsRNAs (cis-nat-dsRNAs)

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“…The testicular innate antiviral responses have been previously demonstrated based on a series of pioneering studies on the expression and regulation of both interferons (IFNs) and antiviral proteins in the testis by Professor Jégou's group. [60][61][62]95,96 These investigators also showed that several defensins are expressed in murine and human testes, and may contribute to the innate antimicrobial defense. 97 Recent studies have revealed that various PRRs are abundantly expressed in testicular cells and initiate testicular innate immune responses.…”

Section: Testicular Innate Immunitymentioning

confidence: 95%

“…59 Previous studies demonstrated that rat Leydig cells exhibit innate antiviral ability in response to viral infection. 60,61 Human Leydig cells show relatively weak antiviral activity compared with rat cells. 62 These observations raise an interesting question whether the human testis has a weaker innate defense system against viral infection compared with the murine testis.…”

Section: Immune Privilege In the Testismentioning

confidence: 99%

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Testicular defense systems: immune privilege and innate immunity

et al. 2014

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The mammalian testis possesses a special immunological environment because of its properties of remarkable immune privilege and effective local innate immunity. Testicular immune privilege protects immunogenic germ cells from systemic immune attack, and local innate immunity is important in preventing testicular microbial infections. The breakdown of local testicular immune homeostasis may lead to orchitis, an etiological factor of male infertility. The mechanisms underlying testicular immune privilege have been investigated for a long time. Increasing evidence shows that both a local immunosuppressive milieu and systemic immune tolerance are involved in maintaining testicular immune privilege status. The mechanisms underlying testicular innate immunity are emerging based on the investigation of the pattern recognition receptor-mediated innate immune response in testicular cells. This review summarizes our current understanding of testicular defense mechanisms and identifies topics that merit further investigation.

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Production of the antiviral proteins 2′5′oligoadenylate synthetase, PKR and Mx in interstitial cells and spermatogonia

Cited by 25 publications

References 13 publications

Excess Type I Interferon Signaling in the Mouse Seminiferous Tubules Leads to Germ Cell Loss and Sterility

Excess Type I Interferon Signaling in the Mouse Seminiferous Tubules Leads to Germ Cell Loss and Sterility

Male germ cells express abundant endogenous siRNAs

Testicular defense systems: immune privilege and innate immunity

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