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Testicular activin and follistatin levels are elevated during the course of experimental autoimmune epididymo – orchitis in mice

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ABSTRACT

Experimental autoimmune epididymo-orchitis (EAEO) is a model of chronic inflammation, induced by immunisation with testicular antigens, which reproduces the pathology of some types of human infertility. Activins A and B regulate spermatogenesis and steroidogenesis, but are also pro-inflammatory, pro-fibrotic cytokines. Expression of the activins and their endogenous antagonists, inhibin and follistatin, was examined in murine EAEO. Adult untreated and adjuvant-treated control mice showed no pathology. All mice immunised with testis antigens developed EAEO by 50 days, characterised by loss of germ cells, immune cell infiltration and fibrosis in the testis, similar to biopsies from human inflamed testis. An increase of total CD45+ leukocytes, comprising CD3+ T cells, CD4 + CD8− and CD4 + CD25+ T cells, and a novel population of CD4 + CD8+ double positive T cells was also detected in EAEO testes. This was accompanied by increased expression of TNF, MCP-1 and IL-10. Activin A and B and follistatin protein levels were elevated in EAEO testes, with peak activin expression during the active phase of the disease, whereas mRNA expression of the inhibin B subunits (Inha and Inhbb) and activin receptor subunits (Acvr1b and Acvr2b) were downregulated. These data suggest that activin–follistatin regulation may play a role during the development of EAEO.

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Relative mRNA expression of Inhba (inhibin βA) (a), Inhbb (inhibin βB) (b), Inha (inhibin α) (c), Acvr1b (activin receptor, type IB) (d) and Acvr2b (activin receptor, type IIB) (e) in testes from untreated, adjuvant control and EAEO mice 30, 50 and 80 days after the first immunisation analysed by quantitative RT-PCR. Gene expression levels were similar between untreated, adjuvant and EAEO testis at 30 days. Data are represented as mean ± SEM of 4–5 animals per group; *P < 0.05, **P < 0.01, ***P < 0.001, all other comparisons are not statistically significant.
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f9: Relative mRNA expression of Inhba (inhibin βA) (a), Inhbb (inhibin βB) (b), Inha (inhibin α) (c), Acvr1b (activin receptor, type IB) (d) and Acvr2b (activin receptor, type IIB) (e) in testes from untreated, adjuvant control and EAEO mice 30, 50 and 80 days after the first immunisation analysed by quantitative RT-PCR. Gene expression levels were similar between untreated, adjuvant and EAEO testis at 30 days. Data are represented as mean ± SEM of 4–5 animals per group; *P < 0.05, **P < 0.01, ***P < 0.001, all other comparisons are not statistically significant.

Mentions: Interestingly, gene expression analysis showed no significant change in activin βA mRNA levels (Inhba) in testes from any groups of animals (Fig. 9a). However, the mRNA levels of the activin βB subunit (Inhbb) and inhibin α subunit (Inha) were decreased in 80 days EAEO testis compared to adjuvant control testes (Fig. 9b and c).


Testicular activin and follistatin levels are elevated during the course of experimental autoimmune epididymo – orchitis in mice
Relative mRNA expression of Inhba (inhibin βA) (a), Inhbb (inhibin βB) (b), Inha (inhibin α) (c), Acvr1b (activin receptor, type IB) (d) and Acvr2b (activin receptor, type IIB) (e) in testes from untreated, adjuvant control and EAEO mice 30, 50 and 80 days after the first immunisation analysed by quantitative RT-PCR. Gene expression levels were similar between untreated, adjuvant and EAEO testis at 30 days. Data are represented as mean ± SEM of 4–5 animals per group; *P < 0.05, **P < 0.01, ***P < 0.001, all other comparisons are not statistically significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5304336&req=5

f9: Relative mRNA expression of Inhba (inhibin βA) (a), Inhbb (inhibin βB) (b), Inha (inhibin α) (c), Acvr1b (activin receptor, type IB) (d) and Acvr2b (activin receptor, type IIB) (e) in testes from untreated, adjuvant control and EAEO mice 30, 50 and 80 days after the first immunisation analysed by quantitative RT-PCR. Gene expression levels were similar between untreated, adjuvant and EAEO testis at 30 days. Data are represented as mean ± SEM of 4–5 animals per group; *P < 0.05, **P < 0.01, ***P < 0.001, all other comparisons are not statistically significant.
Mentions: Interestingly, gene expression analysis showed no significant change in activin βA mRNA levels (Inhba) in testes from any groups of animals (Fig. 9a). However, the mRNA levels of the activin βB subunit (Inhbb) and inhibin α subunit (Inha) were decreased in 80 days EAEO testis compared to adjuvant control testes (Fig. 9b and c).

View Article: PubMed Central - PubMed

ABSTRACT

Experimental autoimmune epididymo-orchitis (EAEO) is a model of chronic inflammation, induced by immunisation with testicular antigens, which reproduces the pathology of some types of human infertility. Activins A and B regulate spermatogenesis and steroidogenesis, but are also pro-inflammatory, pro-fibrotic cytokines. Expression of the activins and their endogenous antagonists, inhibin and follistatin, was examined in murine EAEO. Adult untreated and adjuvant-treated control mice showed no pathology. All mice immunised with testis antigens developed EAEO by 50 days, characterised by loss of germ cells, immune cell infiltration and fibrosis in the testis, similar to biopsies from human inflamed testis. An increase of total CD45+ leukocytes, comprising CD3+ T cells, CD4&thinsp;+&thinsp;CD8&minus; and CD4&thinsp;+&thinsp;CD25+ T cells, and a novel population of CD4&thinsp;+&thinsp;CD8+ double positive T cells was also detected in EAEO testes. This was accompanied by increased expression of TNF, MCP-1 and IL-10. Activin A and B and follistatin protein levels were elevated in EAEO testes, with peak activin expression during the active phase of the disease, whereas mRNA expression of the inhibin B subunits (Inha and Inhbb) and activin receptor subunits (Acvr1b and Acvr2b) were downregulated. These data suggest that activin&ndash;follistatin regulation may play a role during the development of EAEO.

No MeSH data available.


Related in: MedlinePlus