Both 20S and 19S components of proteasome are essential for the meiosis in male mice

The proteasome is an evolutionarily conserved proteolytic complex comprising the 20S core particle and the 19S regulatory particles, which display both common and unique functions across different tissues or organs. Spermatogenesis, a highly complex process, is reported to rely on the proteasome at various stages for regulating protein turnover. To investigate the potential functions of the proteasome during spermatogenesis, we selected the 20S subunit PSMA1 and the 19S regulatory subunit PSMD2 for further investigation. We generated Psma1-EGFP and Psmd2-mCherry knock-in mouse models, and found that both components are expressed in all cell types during spermatogenesis, particularly within the early stage of germ cell development. To further investigate their potential functions, we specially knocked out Psma1 and Psmd2 in germ cells, respectively. Depletion of either PSMA1 or PSMD2 in germ cells resulted in disrupted spermatogenesis, and the complete absence of sperm in the epididymis. Further analysis indicated that the loss of these proteasome components impairs meiotic initiation. A key regulator for the mitosis-meiosis transition, DMRT1, was found to be accumulated in Psma1 or Psmd2 knockout germ cells, which leads to a reduction in STRA8, thereby disrupts the initiation of meiosis. Our studies shed light on the molecular mechanisms that govern meiotic initiation and identify potential genes associated with male infertility.