IL‐10 is highly expressed in the cryptorchid cryptepididymal epithelium: a probable mechanism preventing immune responses against autoantigenic spermatozoa in the epididymal tubule

Veräjänkorva, Esko; Pöllänen, Pasi; Hänninen, Arno; Martikainen, Mika H.; Sundström, Jari; Antola, H.

doi:10.1046/j.1365-2605.2002.00336.x

Cited by 14 publications

(15 citation statements)

References 11 publications

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“…These elevated cytokine levels may also have affected the induction of epididymitis in the VxCTGC group. Although it remains unknown which cell population produces each cytokine after Vx, it was reported that epithelial and myoid cells of the epididymis produce IL-10 and IL-6 respectively, in cryptorchid cryptepididymis (Verajankorva et al 2002). Clinically, the semen IL-6 level is increased in Vx reversal patients (Nandipati et al 2005).…”

Section: Effects Of Vasectomy On Testicular Autoimmunitymentioning

confidence: 99%

Caput epididymitis but not orchitis was induced by vasectomy in a murine model of experimental autoimmune orchitis

Terayama²,

Naito³

et al. 2008

Reproduction

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Immunization of mice with viable syngeneic testicular germ cells (TGC) alone can induce autoimmune responses against autoantigens of both round and elongating spermatids, resulting in the development of experimental autoimmune orchitis (EAO). Histological lesions in this EAO model without an adjuvant are characterized by lymphocytic infiltration into the testes, spermatogenic disturbance, and a complete lack of epididymitis. In this study, we investigated the effects of vasectomy (Vx) on TGC-induced EAO expecting that Vx augments the severity of testicular inflammation in A/J mice. The results showed that mice receiving Vx alone exhibited no significant inflammatory cell response in either the testes or epididymides, and mice receiving shamVxCTGC immunization had EAO with no epididymitis. In sharp contrast, no EAO was found in the testes of any mice receiving VxCTGC immunization. Instead, caput epididymitis involving CD4CT cells, CD8CT cells, B cells, and macrophages were induced in them with striking elevation of the tissue levels of both IL6 and IL10 mRNA. Furthermore, serum autoantibodies induced by shamVxCTGC immunization were reactive with both round (immature) and elongating (mature) spermatids; however, those induced by VxCTGC immunization were specific to acrosomes of mature spermatids and spermatozoa. These unexpected results indicate that Vx may induce the mode by which autoreactive lymphocytes gain access to TGC autoantigens in the epididymides, leading to autoimmune responses against the autoantigens of mature rather than immature spermatids. Reproduction (2008) 135 859-866

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Section: Effects Of Vasectomy On Testicular Autoimmunitymentioning

confidence: 99%

Caput epididymitis but not orchitis was induced by vasectomy in a murine model of experimental autoimmune orchitis

Terayama²,

Naito³

et al. 2008

Reproduction

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“…The approach described in this article was based on the testable presumption that the epididymis, being an epithelial tube filled with immunologically foreign objects, must be balanced between tolerance and activation. There is strong biochemical evidence for such a dynamic balance in the epididymis (e.g., Jrad‐Lamine et al., ), and the presence of numerous cells of immune‐system origin within the epithelium is consistent with this view (Flickinger et al., ; Hermo and Robaire, ; Serre and Robaire, ; Verajankorva et al., ; Da Silva, ). This includes cells that stain for molecules found only in T lymphocytes, monocytes, dendritic cells, and macrophages.…”

Section: Discussionmentioning

confidence: 85%

Primary Cell Cultures for Understanding Rat Epididymal Inflammation

Chapin

Winton

Nowland

et al. 2014

Birth Defects Research Pt B

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Treatment-induced epididymal inflammation and granuloma formation is only an occasional problem in preclinical drug development, but it can effectively terminate the development of that candidate molecule. Screening for backup molecules without that toxicity must be performed in animals (generally rats) that requires at least 2 to 3 weeks of in vivo exposure, a great deal of specially synthesized candidate compound, and histologic examination of the target tissues. We instead hypothesized that these treatments induced proinflammatory gene expression, and so used mixed-cell cultures from the rat epididymal tubule to monitor the induction of proinflammatory cytokines. Cells were exposed for 24 hr and then cytotoxicity was evaluated with the MTS assay and mRNA levels of Interleukin-6 (IL-6) and growth-related oncogene (GRO) were measured. We found that compounds that were more toxic in vivo stimulated a greater induction of IL-6 and GRO mRNA levels in vitro. By relating effective concentrations in vitro with the predicted C(eff), we could rank compounds by their propensity to induce inflammation in rats in vivo. This method allowed the identification of several compounds with very low inflammatory induction in vitro. When tested in rats, the compounds produced small degrees of inflammation at an acceptable margin (approximately 20×), and have progressed into further development.

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“…The role that CD44 plays in ductal branching morphogenesis is not clear, but depends on interaction with hyaluronan [28]. Interestingly, both CD44 and hyaluronan have been found in mammalian adult epididymis and vas deferens [29, 30]. Furthermore, CD44 is required for limb outgrowth [31].…”

Section: Discussionmentioning

confidence: 99%

Changes in Gene Expression during Wolffian Duct Development

Hannema

Print²,

Charnock-Jones

et al. 2006

Horm Res Paediatr

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Background: Wolffian ducts (WDs) are the embryonic precursors of the male reproductive tract. Their development is induced by testosterone, which interacts with the androgen receptor (AR). The molecular pathways underlying androgen-dependent WD development are largely unknown. We aimed to identify AR target genes important in this process. Methods: RNA was isolated from rat WDs at E17.5 and E20.5. Affymetrix GeneChip expression arrays were used to identify transcripts up- or downregulated more than 2-fold. Regulation of seven transcripts was confirmed using quantitative PCR. Results: Transcripts from 76 known genes were regulated, including modulators of insulin-like growth factor and transforming growth factor-βsignalling. By controlling these modulators, androgens may indirectly affect growth factor signalling pathways important in epithelial–mesenchymal interactions and organ development. Caveolin-1, also upregulated, may play a role in modifying as well as mediating AR signalling. Differentiation of WD epithelium and smooth muscle, innervation and extracellular matrix synthesis were reflected in regulation of other transcripts. Several genes were previously suggested to be regulated by androgens or contained functional or putative androgen/glucocorticoid response elements, indicating they may be direct targets of androgen signalling. Conclusion: Our results suggest novel cohorts of signals that may contribute to androgen-dependent WD development and provide hypotheses that can be tested by future studies.

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IL‐10 is highly expressed in the cryptorchid cryptepididymal epithelium: a probable mechanism preventing immune responses against autoantigenic spermatozoa in the epididymal tubule

Cited by 14 publications

References 11 publications

Caput epididymitis but not orchitis was induced by vasectomy in a murine model of experimental autoimmune orchitis

Caput epididymitis but not orchitis was induced by vasectomy in a murine model of experimental autoimmune orchitis

Primary Cell Cultures for Understanding Rat Epididymal Inflammation

Changes in Gene Expression during Wolffian Duct Development

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