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

• DOI: 10.1038/srep42391
• Publication Date: 2017-02-13T11:03:15Z
• Authors: Nour Nicolas; Vera Michel; Sudhanshu Bhushan; Eva Wahle; Susan Hayward; Helen Ludlow; David M. de Kretser; Kate L. Loveland; Hans-Christian Sc...; Andreas Meinhardt; Mark P. Hedger; Monika Fijak
• Keywords: Epididymitis; Inflammation; Male; 0301 basic medicine; Follistatin; 0303 health sciences; Macrophages; T-Lymphocytes; Histocompatibility Antigens Class II; Cell Count; Orchitis; Organ Size; Fibrosis; Article; Actins; Activins; Autoimmune Diseases; 3. Good health; Mice, Inbred C57BL; 03 medical and health sciences; Antigens, CD; Testis; Animals; Cytokines; RNA, Messenger

AbstractExperimental 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 (InhaandInhbb) and activin receptor subunits (Acvr1bandAcvr2b) were downregulated. These data suggest that activin–follistatin regulation may play a role during the development of EAEO.