BMI1 promotes spermatogonia proliferation through epigenetic repression of Ptprm.

Spermatogonia are accountable for spermatogenesis and male fertility, but the underlying mechanisms involved in spermatogonia maintenance are not clear. B lymphoma Mo-MLV insertion region 1 (BMI1) is a key component of epigenetic silencers. BMI1 is essential for stem-cell maintenance. Here, we attempted to uncover the role of BMI1 in spermatogonia maintenance using a mouse spermatogonia cell line (GC-1) and Bmi1-knockout (KO) mouse model. We showed that BMI1 promoted the proliferation and inhibited apoptosis of GC-1 cells. Mechanistically, we present in vitro and in vivo evidence to show that BMI1 binds to the promoter region of the Protein tyrosine phosphatase receptor type M (PTPRM) gene, thereby driving chromatin remodeling and gene silencing. Knockdown of Ptprm expression significantly improved spermatogonia proliferation in BMI1-deficient GC-1 cells. Collectively, our data show, for the first time, an epigenetic mechanism involving in BMI1-mediated gene silencing in spermatogonia maintenance, and provide potential targets for the treatment of male infertility.