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In the adult murine reproductive tract, activin A <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> (<jats:italic>Inhba<\/jats:italic>) expression levels are highest in the caput epididymis and decrease progressively towards the distal vas deferens. The activin\u2010binding protein, follistatin (<jats:styled-content style=\"fixed-case\">FST<\/jats:styled-content>), shows the opposite expression pattern, with exceptionally high levels of the <jats:italic>Fst288 <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> variant in the vas deferens. This unique pattern of expression suggests that activin A and follistatin, in particular <jats:styled-content style=\"fixed-case\">FST<\/jats:styled-content>288, play region\u2010specific roles in regulating the epididymis and vas deferens. The cellular distribution of activin and follistatin and structural organization of the male reproductive tract was examined in wild\u2010type and transgenic (Tgh<jats:styled-content style=\"fixed-case\">FST<\/jats:styled-content>315) mice lacking <jats:styled-content style=\"fixed-case\">FST<\/jats:styled-content>288. Compared to wild\u2010type littermates, Tgh<jats:styled-content style=\"fixed-case\">FST<\/jats:styled-content>315 mice showed a 50% reduction in serum follistatin and a significant elevation of both activin A and B. Testicular, epididymal and seminal vesicle weights were reduced, but intra\u2010testicular testosterone was normal. A decrease in the epididymal duct diameter in the corpus and thickening of the peritubular smooth muscle in the cauda, together with increased coiling of the proximal vas deferens, were observed in Tgh<jats:styled-content style=\"fixed-case\">FST<\/jats:styled-content>315 mice. No immune cell infiltrates were detected. Immunohistochemistry indicated that epithelial cells are the main source of activins and follistatin in the epididymis and vas deferens. Activin A, but not activin B, was also localized to sperm heads in the lumen of the epididymis and vas deferens. Expression of <jats:italic>Inhba<\/jats:italic> and another immunoregulatory gene, indoleamine\u20102,3\u2010dioxygenase (<jats:italic>Ido\u20101<\/jats:italic>), was increased approximately twofold in the Tgh<jats:styled-content style=\"fixed-case\">FST<\/jats:styled-content>315 caput epididymis, but several other genes associated with immunoregulation, inflammation or fibrosis were unaffected. Our novel data indicate that disruption of follistatin expression has significant effects on the testis and epididymis, and suggest an association between activin A and indoleamine\u20102,3\u2010dioxygenase in the caput epididymis, with implications for the epididymal immunoenvironment.<\/jats:p>","DOI":"10.1111\/andr.12337","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T22:32:42Z","timestamp":1487975562000},"page":"578-588","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Activin and follistatin interactions in the male reproductive tract: activin expression and morphological abnormalities in mice lacking follistatin 288"],"prefix":"10.1111","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5584-1371","authenticated-orcid":false,"given":"R.","family":"Wijayarathna","sequence":"first","affiliation":[{"name":"Centre for Reproductive Health Hudson Institute of Medical Research Clayton VIC Australia"},{"name":"Department of Anatomy and Developmental Biology Monash University Clayton VIC Australia"},{"name":"Department of Anatomy and Cell Biology Justus\u2010Liebig University Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. A.","family":"Sarraj","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Health Hudson Institute of Medical Research Clayton VIC Australia"},{"name":"Department of Anatomy and Developmental Biology Monash University Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Genovese","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Health Hudson Institute of Medical Research Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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L.","family":"Loveland","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Developmental Biology Monash University Clayton VIC Australia"},{"name":"School of Clinical Sciences Monash University Monash Medical Centre Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Meinhardt","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Health Hudson Institute of Medical Research Clayton VIC Australia"},{"name":"Department of Anatomy and Developmental Biology Monash University Clayton VIC Australia"},{"name":"Department of Anatomy and Cell Biology Justus\u2010Liebig University Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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