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The essential role of intraflagellar transport protein IFT81 in male mice spermiogenesis and fertility.

子宫内转运蛋白IFT81在雄性小鼠精子生成和生育中的重要作用。

  • 影响因子:3.35
  • DOI:10.1152/ajpcell.00450.2019
  • 作者列表:"Qu W","Yuan S","Quan C","Huang Q","Zhou Q","Yap Y","Shi L","Zhang D","Guest T","Li W","Yee SP","Zhang L","Cazin C","Hess RA","Ray PF","Kherraf ZE","Zhang Z
  • 发表时间:2020-06-01
Abstract

:Intraflagellar transport (IFT) is an evolutionarily conserved mechanism that is indispensable for the formation and maintenance of cilia and flagella; however, the implications and functions of IFT81 remain unknown. In this study, we disrupted IFT81 expression in male germ cells starting from the spermatocyte stage. As a result, homozygous mutant males were completely infertile and displayed abnormal sperm parameters. In addition to oligozoospermia, spermatozoa presented dysmorphic and nonfunctional flagella. Histological examination of testes from homozygous mutant mice revealed abnormal spermiogenesis associated with sloughing of germ cells and the presence of numerous multinucleated giant germ cells (symblasts) in the lumen of seminiferous tubules and epididymis. Moreover, only few elongated spermatids and spermatozoa were seen in analyzed cross sections. Transmission electron microscopy showed a complete disorganization of the axoneme and para-axonemal structures such as the mitochondrial sheath, fibrous sheath, and outer dense fibers. In addition, numerous vesicles that contain unassembled microtubules were observed within developing spermatids. Acrosome structure analysis showed normal appearance, thus excluding a crucial role of IFT81 in acrosome biogenesis. These observations showed that IFT81 is an important member of the IFT process during spermatogenesis and that its absence is associated with abnormal flagellum formation leading to male infertility. The expression levels of several IFT components in testes, including IFT20, IFT25, IFT27, IFT57, IFT74, and IFT88, but not IFT140, were significantly reduced in homozygous mutant mice. Overall, our study demonstrates that IFT81 plays an essential role during spermatogenesis by modulating the assembly and elongation of the sperm flagella.

摘要

: 层内运输 (IFT) 是一种进化上保守的机制,对于纤毛和鞭毛的形成和维持是不可或缺的; 然而,IFT81的含义和功能仍然未知。在这项研究中,我们从精母细胞阶段开始破坏了IFT81在雄性生殖细胞中的表达。结果,纯合突变男性完全不育,并显示出异常的精子参数。除少精子症外,精子呈畸形和无功能性鞭毛。对纯合突变小鼠睾丸的组织学检查显示,精子生成异常与生殖细胞脱落有关,生精小管和附睾腔内存在大量多核巨生殖细胞 (幼细胞)。此外,在分析的横截面中仅观察到少数伸长的精子细胞和精子。透射电镜显示轴突和副轴突结构如线粒体鞘、纤维鞘和外致密纤维完全紊乱。此外,在发育中的精子细胞内观察到许多含有未组装的微管的囊泡。顶体结构分析显示外观正常,因此排除了IFT81在顶体生物发生中的关键作用。这些观察结果表明,IFT81是精子发生过程中IFT过程的重要成员,其缺失与导致男性不育的异常鞭毛形成有关。在纯合子突变小鼠中,睾丸中包括IFT20、IFT25、IFT27、IFT57、IFT74和IFT88但非IFT140的几种IFT组分的表达水平显著降低。总的来说,我们的研究表明IFT81通过调节精子鞭毛的组装和伸长在精子发生过程中起重要作用。

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DOI:10.1080/00498254.2019.1616850
作者列表:["Hekim N","Gure MA","Metin Mahmutoglu A","Gunes S","Asci R","Henkel R"]

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影响因子:1.27
发表时间:2020-01-01
DOI:10.1111/ppc.12392
作者列表:["Safaei Nezhad A","Ebrahimi L","Vakili MM","Kharaghani R"]

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影响因子:2.14
发表时间:2020-02-01
DOI:10.1007/s11427-019-9526-2
作者列表:["Liu D","Yan J","Qiao J"]

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不孕症方向

不孕症分为男性不育和女性不孕,其首要病因诊断依次是:排卵障碍、精液异常、输卵管异常、不明原因的不孕、子宫内膜异位症和其他如免疫学不孕。

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