Study summary · research use only
New aspects of activin biology in epididymal function and immunopathology
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This review with accompanying findings in the mouse male reproductive tract discusses activins (A and B) and their binding protein follistatin in epididymal development, immune regulation, and inflammation. Activin A and B production was largely confined to the initial segment and proximal caput of the epididymis and efferent ducts, while activin A protein was present throughout the epididymis and vas deferens; follistatin was produced in the distal epididymis with high expression in the vas deferens. In situ hybridisation localized activin A mRNA to periductal and interstitial cells and activin B mRNA to periductal cells and epithelial cells of the initial segment; activin A production increased during bacterial epididymitis in mice, promoting inflammation and fibrosis. The authors describe the activin-follistatin balance as important for normal epididymal structure and function.
Abstract
The activins (A and B) and their binding protein, follistatin, play crucial roles in development, immunoregulation and inflammation throughout the body. In the male reproductive tract of the mouse, activin A and B production is largely confined to the initial segment and proximal caput of the epididymis and the efferent ducts, under normal conditions, with very low expression in the corpus, cauda and vas deferens. However, activin A protein is present throughout the epididymis and vas deferens and is largely associated with the epithelium and interstitial macrophages. Conversely, the activin-binding protein follistatin is produced in the distal epididymis, with very high expression in the vas deferens. Activin activity in the distal tract is inhibited by follistatin, and the activin-follistatin balance is important for regulating coiling of the duct during epididymal development. In further experiments, as described in this report, in situ hybridisation was used to localise activin A mRNA principally to cells in the periductal zone and interstitium in the efferent ducts and proximal caput. Activin B mRNA, on the other hand, was localised to periductal cells in the efferent ducts and proximal epididymis and, most notably, to epithelial cells in the initial segment. Activin A is implicated in the regulation of mononuclear phagocyte function and immune responses in the caput and stimulates the expression of the key immunoregulatory protein, indoleamine 2,3-dioxygenase in this region. Activin A production in the corpus and cauda increases dramatically during bacterial epididymitis in mice, promoting inflammation and fibrosis and causing damage to the epithelium and obstruction of the epididymal duct. Consequently, it appears that the activin-follistatin axis is crucial for maintaining normal epididymal structure and function, but disruption of this balance during inflammation has deleterious effects on male fertility. Follistatin has therapeutic potential in ameliorating the proinflammatory and profibrotic effects of activins.
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