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

Nour Nicolas, Vera Michel, Sudhanshu Bhushan, Eva Wahle, Susan Hayward, Helen Ludlow, David M. De Kretser, Kate Loveland, Hans Christian Schuppe, Andreas Meinhardt, Mark P. Hedger, Monika Fijak

Research output: Contribution to journalArticleResearchpeer-review

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 + CD8â ' 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.

Original languageEnglish
Article number42391
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 13 Feb 2017

Cite this

Nicolas, Nour ; Michel, Vera ; Bhushan, Sudhanshu ; Wahle, Eva ; Hayward, Susan ; Ludlow, Helen ; De Kretser, David M. ; Loveland, Kate ; Schuppe, Hans Christian ; Meinhardt, Andreas ; Hedger, Mark P. ; Fijak, Monika. / Testicular activin and follistatin levels are elevated during the course of experimental autoimmune epididymo-orchitis in mice. In: Scientific Reports. 2017 ; Vol. 7.
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title = "Testicular activin and follistatin levels are elevated during the course of experimental autoimmune epididymo-orchitis in mice",
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{\^a} ' 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.",
author = "Nour Nicolas and Vera Michel and Sudhanshu Bhushan and Eva Wahle and Susan Hayward and Helen Ludlow and {De Kretser}, {David M.} and Kate Loveland and Schuppe, {Hans Christian} and Andreas Meinhardt and Hedger, {Mark P.} and Monika Fijak",
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Testicular activin and follistatin levels are elevated during the course of experimental autoimmune epididymo-orchitis in mice. / Nicolas, Nour; Michel, Vera; Bhushan, Sudhanshu; Wahle, Eva; Hayward, Susan; Ludlow, Helen; De Kretser, David M.; Loveland, Kate; Schuppe, Hans Christian; Meinhardt, Andreas; Hedger, Mark P.; Fijak, Monika.

In: Scientific Reports, Vol. 7, 42391, 13.02.2017.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Nicolas, Nour

AU - Michel, Vera

AU - Bhushan, Sudhanshu

AU - Wahle, Eva

AU - Hayward, Susan

AU - Ludlow, Helen

AU - De Kretser, David M.

AU - Loveland, Kate

AU - Schuppe, Hans Christian

AU - Meinhardt, Andreas

AU - Hedger, Mark P.

AU - Fijak, Monika

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N2 - 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 + CD8â ' 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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