Outer dense fibers stabilize the axoneme to maintain sperm motility.
Outer dense fibers stabilize the axoneme to maintain sperm motility.
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外部致密纤维稳定轴丝以维持精子活力
DOI：
10.1111/jcmm.13457
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发表时间：
2018-03
影响因子：
5.3
通讯作者：
Sun F
中科院分区：
文献类型：
--
作者：
Zhao W;Li Z;Ping P;Wang G;Yuan X;Sun F
外周致密纤维作为哺乳动物精子特有的附属结构，被认为在保护精子尾部免受剪切力的作用中起着重要作用。然而，ODF在调节精子运动中的作用和相关机制及其在弱精子症中的病理参与尚不清楚。在这里，我们发现弱精子症患者ODF缺陷的百分比高于对照样本，并且与轴丝缺陷和不活动精子的百分比显著相关。此外，ODF主要成分(ODF1、2、3、4)的表达水平在弱精子症患者中经常下调。有趣的是，ODF大小和精子活力之间存在着跨物种的正相关关系。小鼠Odf2表达的条件性中断导致精子活力降低和弱精子症的特征。同时，Odf2条件基因敲除小鼠和弱精子症患者的精子中乙酰化α-微管蛋白的表达均降低。免疫荧光和生化分析表明，ODF2能与乙酰化的α-微管蛋白结合，保护冷环境中α-微管蛋白的乙酰化水平。最后，我们发现锂提高了ODF家族蛋白和乙酰化α-微管蛋白的表达水平，延长了小鼠的中段长度，并增加了快速运动精子的百分比。我们的结果表明，ODF通过稳定轴丝而有利于精子的运动，ODF家族蛋白的低表达参与了弱精子症的发病机制。锂给药试验将为弱精子症新疗法的开发提供有价值的见解。
Outer dense fibers (ODFs), as unique accessory structures in mammalian sperm, are considered to play a role in the protection of the sperm tail against shear forces. However, the role and relevant mechanisms of ODFs in modulating sperm motility and its pathological involvement in asthenozoospermia were unknown. Here, we found that the percentage of ODF defects was higher in asthenozoospermic samples than that in control samples and was significantly correlated with the percentage of axoneme defects and non‐motile sperm. Furthermore, the expression levels of ODF major components (Odf1, 2, 3, 4) were frequently down‐regulated in asthenozoospermic samples. Intriguingly, the positive relationship between ODF size and sperm motility existed across species. The conditional disruption of Odf2 expression in mice led to reduced sperm motility and the characteristics of asthenozoospermia. Meanwhile, the expression of acetylated α‐tubulin was decreased in sperm from both Odf2 conditional knockout (cKO) mice and asthenozoospermic men. Immunofluorescence and biochemistry analyses showed that Odf2 could bind to acetylated α‐tubulin and protect the acetylation level of α‐tubulin in HEK293T cells in a cold environment. Finally, we found that lithium elevated the expression levels of Odf family proteins and acetylated α‐tubulin, elongated the midpiece length and increased the percentage of rapidly moving sperm in mice. Our results demonstrate that ODFs are beneficial for sperm motility via stabilization of the axoneme and that hypo‐expression of Odf family proteins is involved in the pathogenesis of asthenozoospermia. The lithium administration assay will provide valuable insights into the development of new treatments for asthenozoospermia.
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影响因子：
13.3
作者：
Huang, Ying;Hou, Jia-Kai;Chen, Guo-Qiang
通讯作者：
Chen, Guo-Qiang
错配修复基因的常见变异与精子 DNA 损伤和男性不育风险增加相关
影响因子：
9.3
作者：
Ji G;Long Y;Zhou Y;Huang C;Gu A;Wang X
通讯作者：
Wang X
影响因子：
3.6
作者：
Ferrer, Marvin;Cornwall, Gail;Oko, Richard
通讯作者：
Oko, Richard
影响因子：
2.5
作者：
Fitzgerald, CJ;Oko, RJ;van der Hoorn, FA
通讯作者：
van der Hoorn, FA
DOI：
10.1083/jcb.89.2.309
发表时间：
1981-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Linck RW;Olson GE;Langevin GL
通讯作者：
Langevin GL