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- 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.
authors.affiliation: Department of Anatomy and Cell Biology, Justus-Liebig University, Giessen, Germany.|Hudson Institute of Medical Research, Melbourne, Victoria, Australia.
authors.forename: Nour
authors.initials: N
authors.lastname: Nicolas
authors.affiliation: Department of Anatomy and Cell Biology, Justus-Liebig University, Giessen, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Michel
authors.affiliation: Department of Anatomy and Cell Biology, Justus-Liebig University, Giessen, Germany.
authors.forename: Sudhanshu
authors.initials: S
authors.lastname: Bhushan
authors.affiliation: Department of Anatomy and Cell Biology, Justus-Liebig University, Giessen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Wahle
authors.affiliation: Hudson Institute of Medical Research, Melbourne, Victoria, Australia.
authors.forename: Susan
authors.initials: S
authors.lastname: Hayward
authors.affiliation: Oxford-Brooks University, Oxford, England.
authors.forename: Helen
authors.initials: H
authors.lastname: Ludlow
authors.affiliation: Hudson Institute of Medical Research, Melbourne, Victoria, Australia.|Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: de Kretser
authors.affiliation: Hudson Institute of Medical Research, Melbourne, Victoria, Australia.|School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Loveland
authors.affiliation: Department of Urology, Pediatric Urology and Andrology, Justus-Liebig University, Giessen, Germany.
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Schuppe
authors.affiliation: Department of Anatomy and Cell Biology, Justus-Liebig University, Giessen, Germany.|Hudson Institute of Medical Research, Melbourne, Victoria, Australia.|Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinhardt
authors.affiliation: Hudson Institute of Medical Research, Melbourne, Victoria, Australia.|Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Hedger
authors.affiliation: Department of Anatomy and Cell Biology, Justus-Liebig University, Giessen, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Fijak
mesh_terms: D000199:Actins / Q000378:metabolism; D028341:Activins / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001327:Autoimmune Diseases / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004823:Epididymitis / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D038681:Follistatin / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009920:Orchitis / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D013737:Testis / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C558396:Acta2 protein, mouse; D000199:Actins; D015703:Antigens, CD; D016207:Cytokines; D038681:Follistatin; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D028341:Activins