The Effect Of DAZL Protein On Mouse Sperm Differentiation And Meiosis

Deletions of DAZ(Deleted in AZoospermia)gene account for about 10-15%of infertility in azoospermic or oligospermia men.DAZ family members(DAZ,DAZL and BOULE)encode germ cell-specific RNA binding proteins including one conserved RNA-Recognition Motif(RRM)and DAZ repeat,and are essential for animal gametogenesis.DAZL gene,a member of DAZ family,is conserved from bony fish through humans and is required for development and differentiation of embryonic germ cells.However,the role of DAZL protein during spermatogenesis,in particular spermatid differentiation is largely undetermined.In this study,we found that DAZL and BOULE proteins exhibit an overlapping but distinct expression pattern during murine spermatogenesis,and both DAZL and BOULE proteins are highly expressed in pachytene spermatocytes.Conditional knockout Dazl in early spermatocytes caused male sterility with reduced testis size,and no mature sperm.Spermiogenesis in the mutant mice was arrested at round spermatid(Step 6-8),and the mutant spermatids exhibited a defect in acrosome cap.Furthermore,knockout of both DAZL and BOULE proteins in early spermatocytes results in male infertility and meiotic arrest at diplotene or G2-M phase transition,a remarkably similar phenotype to that of bol mutant fly.Unlike in bol mutant fly,CDC25A expression was not significantly reduced in the mutant mouse.In summary,our study demonstrated that Dazl was essential for mouse spermiogenesis.In mice,DAZL and BOULE are redundant in their function at G2-M phase transition of male meiosis,supporting that DAZ family proteins perform a conserved meiotic function at G2-M phase transition from fly to mice.