Endocrine Abstracts (2012) 29 P1014

Deletion of FSTL3 increases testicular size and delays testicular regression

A. Mukherjee1, K. Oldknow1, J. Seebacher2, J. Villen2, T. Goswami2, S. Gygi2, P. O’Shaughnessy3 & A. Schneyer4

1Royal Veterinary College, London, UK; 2Harvard Medical School, Boston, Massachusetts, USA; 3University of Glasgow, Glasgow, UK; 4Pioneer Valley Life Sciences Institute, University of Massachusetts, Springfield, Massachusetts, USA.

Follistatin-like 3 (FSTL3) is a secreted glycoprotein known to act as an inhibitor of TGFβ ligands such as activin and myostatin. Like activin, FSTL3 is expressed strongly in the testis but the role FSTL3 plays in testis development and physiology is not clearly understood. Here we show that FSTL3 is a key regulator of testicular size and a promoter of age-dependent testicular regression. FSTL3 deletion in mice leads to the development of enlarged testes that show delayed age-related regression. Importantly, testosterone production and spermatogenesis are not altered in FSTL3 KO mice. Increased testicular size in FSTL3 KO mice was associated with increased Sertoli cells and germ cell numbers although Leydig cell numbers were not affected. To identify and investigate molecular pathways contributing to these phenotypes we undertook a quantitative proteomics approach. We find increased AKT signalling, a promoter of cell proliferation, and increased expression of Sirt1, an anti-ageing protein, in FSTL3 KO testis. Survival and maintenance of species depend on timed testicular development and regression, testicular regression being particularly relevant in seasonal breeders. We therefore demonstrate that FSTL3 is a protein that normally blocks inappropriate cellular proliferation in the testis and regulates the maintenance of testicular function.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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