Abstract
Spermatogenesis, which involves mitosis and meiosis of male germ cells, is a highly complicated and coordinately ordered process. Cyclin B1 (CCNB1), an important regulator in cell cycle machinery, is proved essential for mouse embryonic development. However, the role of CCNB1 in mammalian spermatogenesis remains unclear. Here we tested the requirement for CCNB1 using conditional knockout mice lacking CCNB1 in male germ cells. We found that ablation of CCNB1 in gonocytes and spermatogonia led to mouse sterile caused by the male germ cells’ depletion. Gonocyte and spermatogonia without CCNB1 is unable to proliferate normally and apoptosis increased. Moreover, CCNB1 ablation in spermatogonia may promote their differentiation by downregulating Lin28a and upregulating let-7 miRNA. However, ablation of CCNB1 in premeiotic male germ cells did not have an effect on meiosis of spermatocytes and male fertility, suggesting that CCNB1 may be dispensable for meiosis of spermatocytes. Collectively, these results indicate that CCNB1 is critically required for the proliferation of gonocytes and spermatogonia but may be redundant in meiosis of spermatocytes in mouse spermatogenesis.
Highlights
In eukaryotic cells, the onset of M phase is controlled by a common mechanism
We reported the requirement of CCNB1 in spermatogenesis using conditional knockout mice lacking CCNB1 in male germ cells
Ablation of CCNB1 in mouse gonocytes and spermatogonia results in male sterile due to germ cells’ depletion, whereas ablation of CCNB1 in postnatal, premeiotic male germ cells does not have an effect on the meiosis of spermatocyte and male fertility
Summary
The onset of M phase is controlled by a common mechanism. Maturation-promoting factor or M-phase-promoting factor (MPF),[1,2,3,4,5,6,7,8,9] which is composed by cyclin-dependent kinase 1 (CDK1) and cyclin B, governs M-phase entry in eukaryotic cells.[10,11,12,13,14,15,16,17] The activation of MPF requires the dephosphorylation of CDK1 and the association of Cyclin B.18–23 In amphibian, two B-type cyclins, cyclin B1. In the extracts of active Xenopus eggs, ablation of either ccnb[1] or ccnb[2] alone was unable to arrest mitosis, but when both cyclin mRNAs were destroyed, the mitosis events were unable to happen.[11] These results suggest that ccnb[1] and ccnb[2] have redundant roles in the mitosis and meiosis of frog. CCNB1 and CCNB2 were reported to have different localization and expression pattern in mammals,[25,26,27,28] indicating that they may have distinct roles in mitosis and meiosis of mammalian cells. Whether CCNB1 and CCNB2 have distinct roles in mitosis and meiosis of mammalian cells remain unclear
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