UBE2B mRNA alterations are associated with severe oligozoospermia in infertile men.
UBE2B mRNA alterations are associated with severe oligozoospermia in infertile men.
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UBE2B mRNA 改变与不育男性的严重少精症有关。
DOI：
10.1093/molehr/gat008
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发表时间：
2013
影响因子：
4
通讯作者：
Matzuk,MartinM
中科院分区：
文献类型：
--
作者：
Yatsenko,AlexanderN;Georgiadis,AndrewP;Murthy,LataJ;Lamb,DoloresJ;Matzuk,MartinM
少精子症（精子数量低）是一种常见的精液缺乏症。然而，到目前为止，很少有遗传缺陷被确定为导致这种情况。此外，男科诊所可用于少精子症患者的分子遗传诊断测试就更少了。基于对少精子症的动物和基因表达的研究，减数分裂后精子中的几条分子通路可能被破坏。其中一个被破坏的途径是蛋白质泛素化和细胞凋亡。参与该途径的关键蛋白是泛素缀合酶2B，UBE 2B。缺乏Ube 2bin的雄性小鼠会导致生精减数分裂中断，细胞凋亡增加，导致不育。为探讨UBE 2和严重少精子症（0.1-10 × 106个/ml）患者精子mRNA缺陷的相关性，对326例少精子症患者和421例正常精子症患者的精子进行了cDNA测序。在4.6%（15/326）的少精子症患者的精子中发现UBE 2B mRNA的改变，而在对照组中未发现，提示mRNA缺陷与少精子症密切相关（χ2= 19，P= 0.0001）。已鉴定的UBE 2突变包括9个剪接、4个错义和2个无义突变。相应的DNA区域的后续筛选没有发现致病的DNA突变，表明所鉴定的缺陷具有转录后性质。dbSNP数据库中没有报告这些变体，尽管421个对照中有11个（2.6%）存在其他低水平表达的剪接异常。我们的研究结果表明，两种不同的分子机制，mRNA编辑和剪接加工，在少精子症中被破坏。我们推测转录后mRNA缺陷对少精子症的影响可能比以前预期的要大。
Oligozoospermia (low sperm count) is a common semen deficiency. However, to date, few genetic defects have been identified to cause this condition. Moreover, even fewer molecular genetic diagnostic tests are available for patients with oligozoospermia in the andrology clinic. Based on animal and gene expression studies of oligozoospermia, several molecular pathways may be disrupted in post-meiotic spermatozoa. One of the disrupted pathways is protein ubiquitination and cell apoptosis. A critical protein involved in this pathway is the ubiquitin-conjugating enzyme 2B, UBE2B. Absence ofUbe2bin male mice causes spermatogenic meiotic disruption with increased apoptosis, leading to infertility. To examine the association between messenger RNA defects inUBE2Band severe oligozoospermia (0.1–10 × 106cells/ml), sequencing of sperm cDNA in 326 oligozoospermic patients and 421 normozoospermic men was performed. mRNA alterations inUBE2Bwere identified in sperm in 4.6% (15 out of 326) of the oligozoospermic patients, but not found in control men, suggesting strong association between mRNA defects and oligozoospermia (χ2= 19,P= 0.0001). IdentifiedUBE2Balterations include nine splicing, four missense and two nonsense alterations. The follow-up screen of corresponding DNA regions did not reveal causative DNA mutations, suggesting a post-transcriptional nature of identified defects. None of these variants were reported in the dbSNP database, although other splicing abnormalities with low level of expression were present in 11 out of 421 (2.6%) controls. Our findings suggest that two distinct molecular mechanisms, mRNA editing and splicing processing, are disrupted in oligozoospermia. We speculate that the contribution of post-transcriptional mRNA defects to oligozoospermia could be greater than previously anticipated.
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影响因子：
3.5
作者：
Dieterich, Klaus;Zouari, Raoudha;Ray, Pierre F.
通讯作者：
Ray, Pierre F.
DOI：
10.1016/j.juro.2009.12.004
发表时间：
2010-04
期刊：
The Journal of urology
影响因子：
--
作者：
Yatsenko AN;Yatsenko SA;Weedin JW;Lawrence AE;Patel A;Peacock S;Matzuk MM;Lamb DJ;Cheung SW;Lipshultz LI
通讯作者：
Lipshultz LI
影响因子：
158.5
作者：
Guzick, DS;Overstreet, JW;Natl Cooperative Reprod Med Network
通讯作者：
Natl Cooperative Reprod Med Network
DOI：
10.1001/jama.1992.03480130110034
发表时间：
1992-04
期刊：
JAMA
影响因子：
--
作者：
A. Anguiano;R. Oates;J. Amos;Michael Dean;B. Gerrard;C. Stewart;T. Maher;M. White;A. Milunsky-A.
通讯作者：
A. Anguiano;R. Oates;J. Amos;Michael Dean;B. Gerrard;C. Stewart;T. Maher;M. White;A. Milunsky-A.
影响因子：
6.1
作者：
Clementini, E;Palka, C;Tiboni, GM
通讯作者：
Tiboni, GM