Mettl3-mediated m ^6A regulates spermatogonial differentia- tion and meiosis initiation

METTL3 catalyzes the formation of N%methyl-adenosine （m6A） which has important roles in regulating various biological processes. However, the in vivo function of Mettl3 remains largely unknown in mammals. Here we gener- ated germ cell-specific Mettl3 knockout mice and demonstrated that Mettl3 was essential for male fertility and sper- matogenesis. The ablation of Mettl3 in germ cells severely inhibited spermatogonial differentiation and blocked the initiation of meiosis. Transcriptome and m6A profiling analysis revealed that genes functioning in spermatogenesis had altered profiles of expression and alternative splicing. Our findings provide novel insights into the function and regulatory mechanisms of MettD-mediated m6A modification in spermatogenesis and reproduction in mammals.