Deficiency in mouse Y chromosome long arm gene complement is associated with sperm DNA damage.
Deficiency in mouse Y chromosome long arm gene complement is associated with sperm DNA damage.
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DOI：
10.1186/gb-2010-11-6-r66
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发表时间：
2010
期刊：
影响因子：
12.3
通讯作者：
Ward MA
中科院分区：
文献类型：
--
作者：
Yamauchi Y;Riel JM;Stoytcheva Z;Burgoyne PS;Ward MA
具有严重的非PAR Y染色体长臂（NPYq）缺陷的小鼠在体内和体外都是不育的。我们以前已经表明，这些男性的精子，虽然有严重畸形的头部，能够受精卵母细胞通过胞浆内单精子注射（ICSI）和生产活的后代。然而，在持续的ICSI试验中，我们注意到与睾丸精子相比，使用冷冻保存的精子和附睾精子的效率降低。在本研究中，我们测试了NPYq缺乏是否与精子DNA损伤有关-这是ICSI成功率低的已知原因。我们观察到，附睾精子与严重NPYq缺陷（即，删除十分之九或整个NPYq基因互补）的小鼠卵母细胞激活能力受损后ICSI和卵母细胞停滞和父亲染色体断裂的发生率增加。彗星试验显示，这些小鼠的附睾和睾丸精子的DNA损伤增加，附睾精子受到的影响更严重。在所有小鼠中，冷冻增加了DNA损伤水平。来自NPYq严重缺乏小鼠的附睾精子也遭受膜完整性受损和异常染色质凝聚和次优染色质污染。因此，与NPYq缺乏相关的DNA损伤增加可能是染色质重塑紊乱的结果。这项研究提供了NPYq缺陷小鼠精子DNA损伤的第一个证据，并表明NPYq编码的基因可能在调节染色质重塑的过程中发挥作用，从而维持精子DNA的完整性。
Mice with severe non-PAR Y chromosome long arm (NPYq) deficiencies are infertile in vivo and in vitro. We have previously shown that sperm from these males, although having grossly malformed heads, were able to fertilize oocytes via intracytoplasmic sperm injection (ICSI) and yield live offspring. However, in continuing ICSI trials we noted a reduced efficiency when cryopreserved sperm were used and with epididymal sperm as compared to testicular sperm. In the present study we tested if NPYq deficiency is associated with sperm DNA damage - a known cause of poor ICSI success. We observed that epididymal sperm from mice with severe NPYq deficiency (that is, deletion of nine-tenths or the entire NPYq gene complement) are impaired in oocyte activation ability following ICSI and there is an increased incidence of oocyte arrest and paternal chromosome breaks. Comet assays revealed increased DNA damage in both epididymal and testicular sperm from these mice, with epididymal sperm more severely affected. In all mice the level of DNA damage was increased by freezing. Epididymal sperm from mice with severe NPYq deficiencies also suffered from impaired membrane integrity and abnormal chromatin condensation and suboptimal chromatin protamination. It is therefore likely that the increased DNA damage associated with NPYq deficiency is a consequence of disturbed chromatin remodeling. This study provides the first evidence of DNA damage in sperm from mice with NPYq deficiencies and indicates that NPYq-encoded gene/s may play a role in processes regulating chromatin remodeling and thus in maintaining DNA integrity in sperm.
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影响因子：
3.6
作者：
Fernandez-Gonzalez, Raul;Moreira, Pedro Nuno;Gutierrez-Adan, Alfonso
通讯作者：
Gutierrez-Adan, Alfonso
影响因子：
--
作者：
Aoki, VW;Moskovtsev, SI;Carrell, DT
通讯作者：
Carrell, DT
DOI：
10.1159/000014954
发表时间：
1998-01-01
期刊：
CYTOGENETICS AND CELL GENETICS
影响因子：
--
作者：
Burgoyne, PS;Mahadevaiah, SK;Ashworth, A
通讯作者：
Ashworth, A
影响因子：
6.1
作者：
Donnelly, ET;Steele, EK;Lewis, SEM
通讯作者：
Lewis, SEM
影响因子：
3.6
作者：
KIMURA, Y;YANAGIMACHI, R
通讯作者：
YANAGIMACHI, R