title: Activin and follistatin interactions in the male reproductive tract: activin expression and morphological abnormalities in mice lacking follistatin 288.
abstract: Activin A is an important regulator of testicular and epididymal development and function, as well as inflammation and immunity. In the adult murine reproductive tract, activin A mRNA (Inhba) expression levels are highest in the caput epididymis and decrease progressively towards the distal vas deferens. The activin-binding protein, follistatin (FST), shows the opposite expression pattern, with exceptionally high levels of the Fst288 mRNA variant in the vas deferens. This unique pattern of expression suggests that activin A and follistatin, in particular FST288, play region-specific 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-type and transgenic (TghFST315) mice lacking FST288. Compared to wild-type littermates, TghFST315 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-testicular 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 TghFST315 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 Inhba and another immunoregulatory gene, indoleamine-2,3-dioxygenase (Ido-1), was increased approximately twofold in the TghFST315 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-2,3-dioxygenase in the caput epididymis, with implications for the epididymal immunoenvironment.
authors.affiliation: Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC, Australia.|Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia.|Department of Anatomy and Cell Biology, Justus-Liebig University, Giessen, Germany.
authors.forename: R
authors.identifier: 0000-0002-5584-1371
authors.initials: R
authors.lastname: Wijayarathna
authors.affiliation: Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC, Australia.|Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia.
authors.forename: M A
authors.initials: MA
authors.lastname: Sarraj
authors.affiliation: Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Genovese
authors.affiliation: Gynaecology Research Centre, Department of Obstetrics and Gynaecology, The University of Melbourne and Royal Women's Hospital, Parkville, VIC, Australia.
authors.forename: J E
authors.initials: JE
authors.lastname: Girling
authors.affiliation: Department of Anatomy and Cell Biology, Justus-Liebig University, Giessen, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Michel
authors.affiliation: Oxford Brookes University, Oxford, UK.
authors.forename: H
authors.initials: H
authors.lastname: Ludlow
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia.|School of Clinical Sciences, Monash University, Monash Medical Centre, Clayton, VIC, Australia.
authors.forename: K L
authors.identifier: 0000-0002-5750-8046
authors.initials: KL
authors.lastname: Loveland
authors.affiliation: Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC, Australia.|Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia.|Department of Anatomy and Cell Biology, Justus-Liebig University, Giessen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Meinhardt
authors.affiliation: Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC, Australia.|Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia.
authors.forename: D M
authors.initials: DM
authors.lastname: de Kretser
authors.affiliation: Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC, Australia.|Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia.
authors.forename: M P
authors.initials: MP
authors.lastname: Hedger
mesh_terms: D028341:Activins / Q000378:metabolism*; D000818:Animals; D038681:Follistatin / Q000378:metabolism*; D005837:Genitalia, Male / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction
chemical_list: D038681:Follistatin; C479339:follistatin, 288-amino acid isoform; D028341:Activins
keywords: activins; epididymis; follistatin; gene expression; vas deferens