Meiotic prophase abnormalities and metaphase cell death in MLH1-deficient mouse spermatocytes: Insights into regulation of spermatogenic progress
Meiotic prophase abnormalities and metaphase cell death in MLH1-deficient mouse spermatocytes: Insights into regulation of spermatogenic progress
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DOI：
10.1006/dbio.2002.0708
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发表时间：
2002-09-01
影响因子：
2.7
通讯作者：
Handel, MA
中科院分区：
文献类型：
--
作者：
Eaker, S;Cobb, J;Handel, MA
MLH1 蛋白是小鼠正常减数分裂所必需的，它的缺失会导致二价染色体之间配对维持失败、减数分裂异常以及随之而来的两性不育。在本研究中，我们研究了前期染色体上 MLH1 蛋白焦点未能形成是否会导致前期精母细胞被消除，如果不是，单价染色体是否可以在减数分裂纺锤体上正常排列，以及中期精母细胞是否会被延迟和/或消除。尽管不存在MLH1灶，但未检测到前期精母细胞凋亡。事实上，Mlh1(-/-)小鼠的粗线期精母细胞的染色体在体内和体外都能够浓缩中期染色体。大多数浓缩染色体是单价的，具有空间上不同的 FISH 信号。 Mlh1(-/-)精母细胞中发生了典型的中期事件，例如联会复合体分解和组蛋白H3上Ser10的磷酸化，这表明在面对大量染色体异常时，减数分裂中期的开始没有受到抑制。然而，浓缩的单价染色体并未正确排列到大多数 Mlh1(-/-) 精母细胞的纺锤体上。大多数减数分裂中期精母细胞具有双极纺锤体，但染色体以类似中期的模式从微管组织中心辐射出去，而不是实现双极取向。直到减数分裂中期开始后才观察到细胞凋亡。因此，精母细胞不会直接响应最初的减数分裂缺陷而被消除，而是随后被消除。综上所述，这些观察结果表明，纺锤体组装检查点，而不是重组或交叉检查点，可能会因减数分裂错误而被激活，从而确保消除染色体异常的配子前体。 (C) 2002 年爱思唯尔科学（美国）。
The MLH1 protein is required for normal meiosis in mice and its absence leads to failure in maintenance of pairing between bivalent chromosomes, abnormal meiotic division, and ensuing sterility in both sexes. In this study, we investigated whether failure to develop foci of MLH1 protein on chromosomes in prophase would lead to elimination of prophase spermatocytes, and, if not, whether univalent chromosomes could align normally on the meiotic spindle and whether metaphase spermatocytes would be delayed and/or eliminated. In spite of the absence of MLH1 foci, no apoptosis of spermatocytes in prophase was detected. In fact, chromosomes of pachytene spermatocytes from Mlh1(-/-) mice were competent to condense metaphase chromosomes, both in vivo and in vitro. Most condensed chromosomes were univalents with spatially distinct FISH signals. Typical metaphase events, such as synaptonemal complex breakdown and the phosphorylation of Ser10 on histone H3, occurred in Mlh1(-/-) spermatocytes, suggesting that there is no inhibition of onset of meiotic metaphase in the face of massive chromosomal abnormalities. However, the condensed univalent chromosomes did not align correctly onto the spindle apparatus in the majority of Mlh1(-/-) spermatocytes. Most meiotic metaphase spermatocytes were characterized with bipolar spindles, but chromosomes radiated away from the microtubule-organizing centers in a prometaphase-like pattern rather than achieving a bipolar orientation. Apoptosis was not observed until after the onset of meiotic metaphase. Thus, spermatocytes are not eliminated in direct response to the initial meiotic defect, but are eliminated later. Taken together, these observations suggest that a spindle assembly checkpoint, rather than a recombination or chiasmata checkpoint, may be activated in response to meiotic errors, thereby ensuring elimination of chromosomally abnormal gamete precursors. (C) 2002 Elsevier Science (USA).