Research Center for Translational Medicine, Shanghai East Hospital, School of Medicine, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
Cell Death Dis. 2021 May 24;12(6):531. doi: 10.1038/s41419-021-03815-4.
Monopolar spindle 1 (MPS1), which plays a critical role in somatic mitosis, has also been revealed to be essential for meiosis I in oocytes. Spermatogenesis is an important process involving successive mitosis and meiosis, but the function of MPS1 in spermatogenesis remains unclear. Here, we generated Mps1 conditional knockout mice and found that Ddx4-cre-driven loss of Mps1 in male mice resulted in depletion of undifferentiated spermatogonial cells and subsequently of differentiated spermatogonia and spermatocytes. In addition, Stra8-cre-driven ablation of Mps1 in male mice led to germ cell loss and fertility reduction. Spermatocytes lacking Mps1 have blocked at the zygotene-to-pachytene transition in the prophase of meiosis I, which may be due to decreased H2B ubiquitination level mediated by MDM2. And the expression of many meiotic genes was decreased, while that of apoptotic genes was increased. Moreover, we also detected increased apoptosis in spermatocytes with Mps1 knockout, which may have been the reason why germ cells were lost. Taken together, our findings indicate that MPS1 is required for mitosis of gonocytes and spermatogonia, differentiation of undifferentiated spermatogonia, and progression of meiosis I in spermatocytes.
MPS1 是有丝分裂所必需的，它在体细胞核有丝分裂中起着关键作用，也被发现对卵母细胞减数分裂 I 至关重要。精子发生是一个重要的过程，涉及连续的有丝分裂和减数分裂，但 MPS1 在精子发生中的功能尚不清楚。在这里，我们生成了 Mps1 条件性敲除小鼠，并发现 Ddx4-cre 驱动的雄性小鼠中 Mps1 的缺失导致未分化精原细胞的耗竭，随后分化的精原细胞和精母细胞也随之耗竭。此外，Stra8-cre 驱动的雄性小鼠中 Mps1 的缺失导致生殖细胞丢失和生育力降低。缺乏 Mps1 的精母细胞在减数分裂 I 的前期停滞在合线期到粗线期，这可能是由于 MDM2 介导的 H2B 泛素化水平降低所致。许多减数分裂基因的表达减少，而凋亡基因的表达增加。此外，我们还检测到 Mps1 敲除的精母细胞中凋亡增加，这可能是生殖细胞丢失的原因。总之，我们的研究结果表明，MPS1 对于性母细胞和精原细胞的有丝分裂、未分化精原细胞的分化以及精母细胞减数分裂 I 的进展是必需的。
