Increased Sertoli Cell Proliferation and Sperm Production in Follistatin-like 3 (FSTL3) Deleted Mice

Presentation Number: SUN 250
Date of Presentation: April 2nd, 2017

Randy Ballesteros*1 and Abir Mukherjee2
1Royal Veterinary College, London, UNITED KINGDOM, 2Royal Veterinary College, London, United Kingdom


Currently, 1 in 10 couples are infertile and about a third of this is due to male infertility. Notwithstanding the world population, infertility is extremely deleterious to the emotional wellbeing and quality of life of affected couples. The causes and mechanisms of male infertility are complex and new therapies need to be found. Only one spermatozoon is needed to fertilise an oocyte yet mammalian male fecundity depends on the production of large numbers of spermatozoa. The number of spermatozoa produced depends on the number of Sertoli cells in the seminiferous tubule. Activin and related TGFβ family ligands are among the factors that regulate testicular development and function. Activin action is regulated by FSTL3, an endogenous glycoprotein that binds and inhibits activin. We have shown that global FSTL3 deletion in mice leads to increased adult testicular size with concurrent increase in Sertoli and germ cell numbers. Interestingly, testicular mass regression observed during ageing in wild-type (WT) males is prevented in FSTL3 deficient (FSTL3 KO) mice. Here we test whether Sertoli cell number or proliferation, or both, is increased in FSTL3 KO mice. Strikingly, the FSTL3 KO testicular size/body ratio is similar to WT at weaning (3 weeks) but 1.5 fold increased by 17 weeks. Hence, while Sertoli cell number is similar between the two genotypes early in life, with age the number of Sertoli cells and hence the germ cell components of the FSTL3 KO mice increase compared to WT. To begin to investigate testicular cell proliferation we monitored PCNA expression in FSTL3 and WT testes at 3 weeks (prior to the onset of the first wave of spermatogenesis) and 8 weeks (adult). While PCNA expression at 8 weeks is similar between the two genotypes, at 3 weeks FSTL3 KO mice showed significantly increased testicular expression of PCNA compared to WT. Also, while sperm count is similar in adult mice (38 weeks), FSTL3 KO mice have an 8 fold greater sperm count, compared to WT, in aged (91 weeks) mice. Also, sperm count in FSTL3 KO mice does not change between the two age groups. Taken together, our findings support the hypothesis that Sertoli cell proliferation is increased beyond the stages of somatic expansion in FSTL3 gene deleted mice and sperm count is higher in aged FSTL3 KO mice. Both of these phenotypes are associated with improved male fertility. Currently we are testing whether sperm traits are normal and whether sperm function is enhanced in FSTL3 KO mice.


Nothing to Disclose: RB, AM