Activation of Toll like receptor 3 induces spermatogonial stem cell apoptosis

Hu, Jianxin; Song, Dalong; Luo, Guangheng; Xu, Suzhong; Cao, Ying; Sun, Zhaolin

doi:10.1002/cbf.3133

Cited by 5 publications

(3 citation statements)

References 21 publications

(38 reference statements)

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“…In contrast, Sendai virus (SeV) (136), MuV (746) and ZIKV (581) infection did not trigger an IFN-based antiviral response in differentiating rat and mouse germ cells. Nevertheless, poly IC induced the production of pro-inflammatory cytokines and type I IFN through TLR3 and MDA5 signaling in mouse germ cells, but to a much lower level than in Leydig cells (302,724). Exogenous IFN stimulation failed to induce a strong upregulation of ISGs in differentiating testicular germ cells, which is in line with the lack of functional type I IFN receptor expression in meiotic and post-meiotic mouse germ cells (136,581,602).…”

Section: Rodent Modelsmentioning

confidence: 68%

From Ancient to Emerging Infections: The Odyssey of Viruses in the Male Genital Tract

Tortorec

Matusali

Mahé

et al. 2020

Physiological Reviews

103

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The male genital tract (MGT) is the target of a number of viral infections that can have deleterious consequences at the individual, offspring, and population levels. These consequences include infertility, cancers of male organs, transmission to the embryo/fetal development abnormalities, and sexual dissemination of major viral pathogens such as human immunodeficiency virus (HIV) and hepatitis B virus. Lately, two emerging viruses, Zika and Ebola, have additionally revealed that the human MGT can constitute a reservoir for viruses cleared from peripheral circulation by the immune system, leading to their sexual transmission by cured men. This represents a concern for future epidemics and further underlines the need for a better understanding of the interplay between viruses and the MGT. We review here how viruses, from ancient viruses that integrated the germline during evolution through old viruses (e.g., papillomaviruses originating from Neanderthals) and more modern sexually transmitted infections (e.g., simian zoonotic HIV) to emerging viruses (e.g., Ebola and Zika) take advantage of genital tract colonization for horizontal dissemination, viral persistence, vertical transmission, and endogenization. The MGT immune responses to viruses and the impact of these infections are discussed. We summarize the latest data regarding the sources of viruses in semen and the complex role of this body fluid in sexual transmission. Finally, we introduce key animal findings that are relevant for our understanding of viral infection and persistence in the human MGT and suggest future research directions.

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Section: Rodent Modelsmentioning

confidence: 68%

From Ancient to Emerging Infections: The Odyssey of Viruses in the Male Genital Tract

Tortorec

Matusali

Mahé

et al. 2020

Physiological Reviews

103

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“…Briefly, an in vitro study revealed that Tlr3 activation by polyinosinic-polycytidylic acid, induced apoptosis of spermatogonia (Hu et al 2015). In addition, a study using Tlr2-and Tlr4-deficient mice showed that Tlr2 and Tlr4 contribute to the formation of autoimmune orchitis (Liu et al 2015).…”

Section: Discussionmentioning

confidence: 99%

BXSB/MpJ-Yaa mouse model of systemic autoimmune disease shows increased apoptotic germ cells in stage XII of the seminiferous epithelial cycle

et al. 2020

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In mammals, the reproductive system and autoimmunity regulate mutual functions. Importantly, systemic autoimmune diseases are thought to cause male infertility, but the underlying pathological mechanism remains unclear. In this study, the morpho-function of the testes in BXSB/MpJ-Yaa mice were analyzed as a representative mouse model for systemic autoimmune diseases to investigate the effect of excessive autoimmunity on spermatogenesis. At 12 and 24 weeks of age, BXSB/MpJ-Yaa mice showed splenomegaly and increased levels of serum autoantibodies, whereas no controls showed similar autoimmune condition. In histological analysis, the enlarged lumen of the seminiferous tubules accompanied with scarce spermatozoa in the epididymal ducts were observed in some of the BXSB/MpJ-Yaa and BXSB/MpJ mice, but not in C57BL/6N mice. Histoplanimetrical analysis revealed significantly increased residual bodies and apoptotic germ cells in the seminiferous tubules in BXSB/MpJ-Yaa testes without apparent inflammation. Notably, in stage XII of the seminiferous epithelial cycles, the apoptotic germ cell number was remarkably increased, showing a significant correlation with the indices of systemic autoimmune disease in BXSB/MpJ-Yaa mice. Furthermore, the Sertoli cell number was reduced at the early disease stage, which likely caused subsequent morphological changes in BXSB/MpJ-Yaa testes. Thus, our histological study revealed the altered morphologies of BXSB/MpJ-Yaa testes, which were not observed in controls, and statistical analysis suggested the effects of an autoimmune condition on this phenotype, particularly the apoptosis of meiotic germ cells. BXSB/MpJ-Yaa mice were shown to be an efficient model to study the relationship between systemic autoimmune disease and the local reproductive system.

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“…By measuring apoptosis using the Annexin V, PI staining and TUNEL assay, our current results show values of the HU-treated groups were consistently higher than that of the control. A recent study found out that Toll like receptor 3/interferon regulatory factor 3 facilitated Fas ligand expression and induced apoptosis in spermatogonial stem cells (30). In another study, testicular germ cells of DBA/C57BL mice administered HU significantly increased expression of Fas, Fas ligand, Caspase-3, Caspase-8 and Caspase-9 related to apoptosis (31).…”

Section: Discussionmentioning

confidence: 99%

Development of a Test Method for the Evaluation of DNA Damage in Mouse Spermatogonial Stem Cells

Jeon

Kim

et al. 2017

ToxicolRes

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Although alternative test methods based on the 3Rs (Replacement, Reduction, Refinement) are being developed to replace animal testing in reproductive and developmental toxicology, they are still in an early stage. Consequently, we aimed to develop alternative test methods in male animals using mouse spermatogonial stem cells (mSSCs). Here, we modified the OECD TG 489 and optimized the in vitro comet assay in our previous study. This study aimed to verify the validity of in vitro tests involving mSSCs by comparing their results with those of in vivo tests using C57BL/6 mice by gavage. We selected hydroxyurea (HU), which is known to chemically induce male reproductive toxicity. The 50% inhibitory concentration (IC50) value of HU was 0.9 mM, as determined by the MTT assay. In the in vitro comet assay, % tail DNA and Olive tail moment (OTM) after HU administration increased significantly, compared to the control. Annexin V, PI staining and TUNEL assays showed that HU caused apoptosis in mSSCs. In order to compare in vitro tests with in vivo tests, the same substances were administered to male C57BL/6 mice. Reproductive toxicity was observed at 25, 50, 100, and 200 mg/kg/day as measured by clinical measures of reduction in sperm motility and testicular weight. The comet assay, DCFH-DA assay, H&E staining, and TUNEL assay were also performed. The results of the test with C57BL/6 mice were similar to those with mSSCs for HU treatment. Finally, linear regression analysis showed a strong positive correlation between results of in vitro tests and those of in vivo. In conclusion, the present study is the first to demonstrate the effect of HU-induced DNA damage, ROS formation, and apoptosis in mSSCs. Further, the results of the current study suggest that mSSCs could be a useful model to predict male reproductive toxicity.

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Activation of Toll like receptor 3 induces spermatogonial stem cell apoptosis

Cited by 5 publications

References 21 publications

From Ancient to Emerging Infections: The Odyssey of Viruses in the Male Genital Tract

From Ancient to Emerging Infections: The Odyssey of Viruses in the Male Genital Tract

BXSB/MpJ-Yaa mouse model of systemic autoimmune disease shows increased apoptotic germ cells in stage XII of the seminiferous epithelial cycle

Development of a Test Method for the Evaluation of DNA Damage in Mouse Spermatogonial Stem Cells

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