The essential roles of Mps1 in spermatogenesis and fertility in mice

被引:11
作者
Fang, Qiang [1 ]
Chen, Xue-Lin [1 ]
Zhang, Lei [1 ]
Li, Ya-Bin [1 ]
Sun, Tian-Zeng [1 ]
Yang, Chen-Xin [1 ]
Chang, Jian-Feng [1 ]
Yang, Xiao-Mei [1 ]
Sun, Feng [1 ]
机构
[1] Tongji Univ, Res Ctr Translat Med, Sch Life Sci & Technol, Shanghai East Hosp,Sch Med, Shanghai 200092, Peoples R China
基金
国家重点研发计划;
关键词
SPINDLE ASSEMBLY CHECKPOINT; MEIOTIC RECOMBINATION; MOUSE; KINETOCHORES; KINASES; CDC20; APC/C; CELLS;
D O I
10.1038/s41419-021-03815-4
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页数:13
相关论文
共 50 条
[21]   Two LXXLL motifs in the N terminus of Mps1 are required for Mps1 nuclear import during G2/M transition and sustained spindle checkpoint responses [J].
Zhang, Xiaojuan ;
Yin, Qingqing ;
Ling, Youguo ;
Zhang, Yanhong ;
Ma, Runlin ;
Ma, Qingjun ;
Cao, Cheng ;
Zhong, Hui ;
Liu, Xuedong ;
Xu, Quanbin .
CELL CYCLE, 2011, 10 (16) :2742-2750
[22]   TC Mps1 12, a novel Mps1 inhibitor, suppresses the growth of hepatocellular carcinoma cells via the accumulation of chromosomal instability [J].
Choi, Minji ;
Min, Yoo Hong ;
Pyo, Jaehyuk ;
Lee, Chang-Woo ;
Jang, Chang-Young ;
Kim, Ja-Eun .
BRITISH JOURNAL OF PHARMACOLOGY, 2017, 174 (12) :1810-1825
[23]   Mps1/TTK: a novel target and biomarker for cancer [J].
Xie, Yuan ;
Wang, Anqiang ;
Lin, Jianzhen ;
Wu, Liangcai ;
Zhang, Haohai ;
Yang, Xiaobo ;
Wan, Xueshuai ;
Miao, Ruoyu ;
Sang, Xinting ;
Zhao, Haitao .
JOURNAL OF DRUG TARGETING, 2017, 25 (02) :112-118
[24]   Mps1 as a Link Between Centrosomes and Genomic Instability [J].
Kasbek, Christopher ;
Yang, Ching-Hui ;
Fisk, Harold A. .
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, 2009, 50 (08) :654-665
[25]   Development of MPS1 Inhibitors: Recent Advances and Perspectives [J].
Zeng, Yangjie ;
Ren, Xiaodong ;
Jin, Pengyao ;
Zhang, Yali ;
Zhuo, Ming ;
Wang, Jubo .
JOURNAL OF MEDICINAL CHEMISTRY, 2023, 66 (24) :16484-16514
[26]   Centriole assembly and the role of Mps1: defensible or dispensable? [J].
Amanda N Pike ;
Harold A Fisk .
Cell Division, 6
[27]   Lactate dehydrogenase a-like 6B is not essential for spermatogenesis and male fertility in mice [J].
Huang, Xueying ;
Wu, Zhicheng ;
Ren, Peng ;
Wu, Yi ;
Lin, Changdong ;
Zhu, Hongwen ;
Dai, Peng .
GENE, 2025, 936
[28]   Mps1 promotes poleward chromosome movements in meiotic prometaphase [J].
Meyer, Regis E. ;
Tipton, Aaron R. ;
LaVictoire, Rebecca ;
Gorbsky, Gary J. ;
Dawson, Dean S. .
MOLECULAR BIOLOGY OF THE CELL, 2021, 32 (10) :1020-1032
[29]   Mps1 is SUMO-modified during the cell cycle [J].
Restuccia, Agnese ;
Yang, Feikun ;
Chen, Changyan ;
Lu, Lou ;
Dai, Wei .
ONCOTARGET, 2016, 7 (03) :3158-3170
[30]   Ablation of the spindle assembly checkpoint by a compound targeting Mps1 [J].
Schmidt, M ;
Budirahardja, Y ;
Klompmaker, R ;
Medema, RH .
EMBO REPORTS, 2005, 6 (09) :866-872