ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2017) 50 OC5.1 | DOI: 10.1530/endoabs.50.OC5.1

Increased sertoli cell proliferation and sperm production in FSTL3 deleted mice

Randy Ballesteros Mejia & Abir Mukherjee


Comparative Biomedical Sciences, Royal Veterinary College, University of London, London, UK.


Male problems such as oligospermia, azoospermia among others, affect around 30% of infertile couples. Male fecundity relies on the production of large numbers of spermatozoa which is dependent on the number of Sertoli cells. Activin and related TGFβ family ligands regulate testicular development and function. Follistatin Like-3 (FSTL3) is a glycoprotein that binds and inhibits activin. FSTL3 deletion in mice leads to increased adult testicular size with concurrent increase in Sertoli and germ cell numbers. Also age-related testicular regression is delayed in FSTL3 KO mice. Our current investigation show that the testicular size/body ratio of FSTL3 KO mice is similar to WT at weaning (3 weeks) but 1.5 fold increased by 17 weeks. We therefore hypothesized that, while Sertoli cell number is similar between the two genotypes early in life, with age the number of Sertoli cells and concomitantly the germ cell components of the FSTL3 KO mice increase compared to WT. To begin to investigate testicular cell proliferation we performed BrdU incorporation and monitored PCNA expression in FSTL3 KO and WT testes before (3 week) and after (8 week) the onset of the first wave of spermatogenesis. Whereas BrdU incorporation and PCNA expression at 8 weeks is similar between the two genotypes, at 3 weeks FSTL3 KO mice showed significantly increased incorporation of BrdU and expression of PCNA compared to WT. In addition, while sperm count is similar in mice aged 38 weeks from both genotypes, there is an 8 fold greater sperm count in FSTL3 KO mice aged 91 weeks compared to their WT counterpart. Taken together, our findings therefore support the idea that FSTL3 deletion leads to Sertoli cell proliferation beyond the stages of somatic expansion compared to WT mice. Currently we are investigating whether these phenotypes are associated with improved male fertility.

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