Testicular activin and follistatin levels are elevated during the course of experimental autoimmune epididymo–orchitis in mice
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
DOI:
10.1038/srep42391
Publication Date:
2017-02-13T11:03:15Z
AUTHORS (12)
ABSTRACT
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.
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