Hamer G, Novak I, Kouznetsova A, Höög C
Department of Cell and Molecular Biology, Karolinska Institute, Berzelius väg 35, Stockholm, SE-171 77, Sweden.
Theriogenology. 2008 Feb;69(3):333-9. doi: 10.1016/j.theriogenology.2007.09.029. Epub 2007 Nov 7.
During meiosis, DNA replication is followed by two successive rounds of chromosome segregation (meiosis I and II), 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(-/-), Smc1beta(-/-) and Sycp3/Sycp1 and Sycp3/Smc1beta 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.
在减数分裂过程中，DNA复制之后是两轮连续的染色体分离（减数分裂I和II），这会产生基因多样化的单倍体配子。第一次减数分裂的前期受到高度调控，同源染色体在此阶段的排列和联会由联会复合体介导。联会复合体的错误组装会导致细胞死亡、减数分裂重组受损和非整倍体。具有减数分裂缺陷的卵母细胞通常能在第一次减数分裂前期存活下来，并产生非整倍体配子。另一方面，受到类似影响的精母细胞几乎总是在男性特异性减数分裂检查点发生凋亡，该检查点特别位于精子发生过程中的上皮细胞IV期。对于几种DNA修复或减数分裂重组被消除的基因敲除小鼠模型，已经描述了许多这种IV期特异性停滞的例子。有趣的是，在秀丽隐杆线虫中，减数分裂重组和联会由两个独立的检查点途径监测。因此，我们研究了几种在减数分裂配对和联会方面存在特异性缺陷的基因敲除小鼠（Sycp1(-/-)、Sycp3(-/-)、Smc1beta(-/-)以及Sycp3/Sycp1和Sycp3/Smc1beta双敲除小鼠）的精子发生过程。与重组缺陷的情况一样，我们发现所有这些基因型也都在上皮细胞IV期特异性停滞。似乎上皮细胞IV期检查点会清除那些未能通过某种质量检查的精母细胞，这种质量检查与联会或DNA损伤有关。
