Damaged spermatogenic cells induce inflammatory gene expression in mouse Sertoli cells through the activation of Toll-like receptors 2 and 4

Zhang, Xiaoyan; Wang, Tao; Deng, Tingting; Xiong, Wenyong; Lui, Peng; Li, Nan; Chen, Yongmei; Han, Daishu

doi:10.1016/j.mce.2012.10.016

Cited by 59 publications

(60 citation statements)

References 63 publications

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“…The observed enrichment of the immunological response genes was likely to be a consequence of the increased germ‐cell apoptosis observed in the E2F1 −/− ‐testis. An increased amount of damaged spermatogenic cell products and germ‐cell apoptosis trigger the secretion of inflammatory cytokines by SCs and attract macrophages to the testis (Zhang et al ., 2013). …”

Section: Discussionmentioning

confidence: 99%

E2F1 controls germ cell apoptosis during the first wave of spermatogenesis

et al. 2015

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SummaryCell cycle control during spermatogenesis is a highly complex process owing to the control of the mitotic expansion of the spermatogonial cell population and following meiosis, induction of DNA breaks during meiosis and the high levels of physiological germ‐cell apoptosis. We set out to study how E2F1, a key controller of cell cycle, apoptosis, and DNA damage responses, functions in the developing and adult testis. We first analyzed the expression pattern of E2f1 during post‐natal testis development using RNA in situ hybridization, which showed a differential expression pattern of E2f1 in the adult and juvenile mouse testes. To study the function of E2f1, we took advantage of the E2F1−/− mouse line, which was back‐crossed to C57Bl/6J genetic background. E2f1 loss led to a severe progressive testicular atrophy beginning at the age of 20 days. Spermatogonial apoptosis during the first wave of spermatogenesis was decreased. However, already in the first wave of spermatogenesis an extensive apoptosis of spermatocytes was observed. In the adult E2F1−/− testes, the atrophy due to loss of spermatocytes was further exacerbated by loss of spermatogonial stem cells. Surprisingly, only subtle changes in global gene expression array profiling were observed in E2F1−/− testis at PND20. To dissect the changes in each testicular cell type, an additional comparative analysis of the array data was performed making use of previously published data on transcriptomes of the individual testicular cell types. Taken together, our data indicate that E2F1 has a differential role during first wave of spermatogenesis and in the adult testis, which emphasizes the complex nature of cell cycle control in the developing testis.

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Section: Discussionmentioning

confidence: 99%

E2F1 controls germ cell apoptosis during the first wave of spermatogenesis

et al. 2015

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“…Regarding SCs, previous studies have reported that the immunoreaction products for immunoreactive AvBD11 were found in the cytoplasm of rooster SCs (Watanabe et al 2011), while mouse SCs express members of the Tlr family (Tlr3, Tlr6, and Tlr7, but not Tlr8, Tlr9, and Tlr11; Wu et al 2008), which can initiate testicular local innate immune responses by increasing expression of cytokines (Riccioli et al 2006, Starace et al 2008, Wu et al 2008, Zhang et al 2013. However, as TLR expression changes in relation to the pathogen involved, the cellular patterns of TLR expression vary in species, and the results obtained after TLR stimulation in one species may not be predictive of what will occur in another species (Akira & Takeda 2004).…”

Section: Discussionmentioning

confidence: 99%

Activation of innate immune system in response to lipopolysaccharide in chicken Sertoli cells

Michailidis¹,

Anastasiadou²,

Guibert³

et al. 2014

Reproduction

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Sertoli cells (SCs) play an important physiological role in the testis, as they support, nourish, and protect the germ cells. As protection of the developing spermatozoa is an emerging aspect of reproductive physiology, this study examined the expression pattern of innate immune-related genes, including avian b-defensins (AvBDs), Toll-like receptors (TLRs), and cytokines, and investigated the time course of an inflammatory response in rooster SCs triggered by exposure to the bacterial endotoxin lipopolysaccharide (LPS). SCs were isolated from 6-week-old chicken, cultured in vitro, and stimulated with 1 mg/ml LPS at different time courses (0, 6, 12, 24, and 48 h). Data on expression analysis revealed that all ten members of the chicken TLR family, nine members of the AvBD family, as well as eight cytokine genes were expressed in SCs. Quantitative real-time PCR analysis revealed that LPS treatment resulted in significant induction of the expression levels of six TLRs, six AvBDs, and four cytokine genes, while two cytokine genes were downregulated and two other genes were unchanged. The increasing interleukin 1b (IL1b) production was confirmed in the conditioned medium. Furthermore, the phagocytosis of SCs was increased after LPS treatment. In conclusion, these findings provide evidence that SCs express innate immunerelated genes and respond directly to bacterial ligands. These genes represent an important component of the immune system, which could be integrated into semen, and present a distinctive constituent of the protective repertoire of the testis against ascending infections.

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“…29 We recently demonstrated that damaged germ cells induce inflammatory responses in the testis. 30 Therefore, timely removal of apoptotic germ cells and residual bodies by the SCs is important to avoid autoimmune responses.…”

Section: Immune Privilege In the Testismentioning

confidence: 99%

“…We recently demonstrated that damaged germ cells induce endogenous inflammatory responses in the testis. 30 Therefore, the Gas6/ProS-TAM system plays roles in maintaining testicular homeostasis by inhibiting local innate immune responses and facilitating the clearance of auto-antigens.…”

Section: Immune Privilege In the Testismentioning

confidence: 99%

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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Damaged spermatogenic cells induce inflammatory gene expression in mouse Sertoli cells through the activation of Toll-like receptors 2 and 4

Cited by 59 publications

References 63 publications

E2F1 controls germ cell apoptosis during the first wave of spermatogenesis

E2F1 controls germ cell apoptosis during the first wave of spermatogenesis

Activation of innate immune system in response to lipopolysaccharide in chicken Sertoli cells

Testicular defense systems: immune privilege and innate immunity

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