Disruption of pairing and synapsis of chromosomes causes stage-specific apoptosis of male meiotic cells
Disruption of pairing and synapsis of chromosomes causes stage-specific apoptosis of male meiotic cells
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DOI：
10.1016/j.theriogenology.2007.09.029
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发表时间：
2008-02-01
期刊：
影响因子：
2.8
通讯作者：
Hoog, C.
中科院分区：
文献类型：
--
作者：
Hamer, G.;Novak, I.;Hoog, C.
在减数分裂期间，DNA复制之后是两轮连续的染色体分离（减数分裂I和11），这产生了遗传多样性的单倍体配子。第一次减数分裂的前期是高度调节的，在这个阶段同源染色体的排列和联会是由联会复合体介导的。联会复合体的不正确组装导致细胞死亡、减数分裂重组受损和非整倍性。有减数分裂缺陷的卵母细胞通常在第一次减数分裂前期存活，并产生非整倍体配子。另一方面，同样受影响的精母细胞几乎总是在雄性特异性减数分裂检查点发生凋亡，该检查点位于精子发生过程中的上皮IV期。这种阶段IV特异性停滞的许多例子已经在几种遗传小鼠模型中描述，其中DNA修复或减数分裂重组被废除。有趣的是，在线虫中，减数分裂重组和突触是由两个独立的检查点途径监测的。因此，我们研究了几种基因敲除小鼠（Sycp 1（-/-），Sycp 3（-/-），Smcl β（-/-）和Sycp 3/Sycp 1和Sycp 3/Smc 1 β双敲除）的精子发生，这些小鼠在减数分裂配对和突触中有特异性缺陷。与重组缺陷一样，我们发现所有这些基因型也特异性地停滞在上皮IV期。似乎上皮IV期检查点消除了未通过某种质量检查的精母细胞，这与突触或DNA损伤有关。(C)2008年爱思唯尔公司All rights reserved.
During meiosis, DNA replication is followed by two successive rounds of chromosome segregation (meiosis I and 11), which give rise to genetically diverse haploid gametes. The prophase of the first meiotic division is highly regulated and alignment and synapsis of the homologous chromosomes during this stage are mediated by the synaptonemal complex. Incorrect assembly of the synaptonemal complex results in cell death, impaired meiotic recombination and aneuploidy. Oocytes with meiotic defects often survive the first meiotic prophase and give rise to aneuploid gametes. Similarly affected spermatocytes, on the other hand, almost always undergo apoptosis at a male-specific meiotic checkpoint, located specifically at epithelial stage IV during spermatogenesis. Many examples of this stage IV-specific arrest have been described for several genetic mouse models in which DNA repair or meiotic recombination are abrogated. Interestingly, in C elegans, meiotic recombination and synapsis are monitored by two separate checkpoint pathways. Therefore we studied spermatogenesis in several knockout mice (Sycp1(-/-), Sycp3(-/-), Smcl beta(-/-) and Sycp3/Sycp1 and Sycp3/Smc1 beta double-knockouts) that are specifically defective in meiotic pairing and synapsis. Like for recombination defects, we found that all these genotypes also specifically arrest at epithelial stage IV. It seems that the epithelial stage IV checkpoint eliminates spermatocytes that fail a certain quality check, being either synapsis or DNA damage related. (C) 2008 Elsevier Inc. All rights reserved.