Motile cilia of the male reproductive system require miR-34/miR-449 for development and function to generate luminal turbulence
Motile cilia of the male reproductive system require miR-34/miR-449 for development and function to generate luminal turbulence
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男性生殖系统的运动纤毛需要 miR-34/miR-449 来发育和发挥功能以产生管腔湍流
DOI：
10.1073/pnas.1817018116
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发表时间：
2019-01
影响因子：
11.1
通讯作者：
Yan Wei
中科院分区：
文献类型：
--
作者：
Yuan Shuiqiao;Liu Yue;Peng Hongying;Tang Chong;Hennig Grant W.;Wang Zhuqing;Wang Li;Yu Tian;Klukovich Rachel;Zhang Ying;Zheng Huili;Xu Chen;Wu Jingwen;Hess Rex A.;Yan Wei
意义运动纤毛排列在呼吸系统和生殖系统，以及大脑和脊柱上，协调的节拍使液体在腔表面移动。研究表明，睫状体结构或搏动模式的破坏与许多称为睫状体病的疾病有关。多年来，人们一直认为男性生殖系统中的纤毛搏动通过微小的输出小管将精子从睾丸推向附睾。在这里，我们表明，运动纤毛内衬的传出小管不直接推动精子，而是作为搅拌器，产生剧烈的流体湍流，以保持悬浮液的精子内的管腔流体，从而确保平衡的流体重吸收的无纤毛细胞。纤毛是细胞表面，微管为基础的细胞器，突出到细胞外空间。运动纤毛在整个真核生物中是保守的，它们的跳动诱导流体相对于细胞表面的流动。在哺乳动物中，运动纤毛的协调跳动提供了与腔内容物的运动相关的高度专门化的功能，如在呼吸道中运输粘液的异时波所见。运动纤毛也存在于男性和女性生殖道。在雌性中，输卵管纤毛的波浪状运动将卵母细胞和胚胎运送到子宫。男性传出小管中的运动纤毛也具有类似的功能，即，将不动的精子从睾丸网运送到附睾。然而，我们在这里报告，男性的传出导管纤毛不显示一个统一的波浪状节拍，只在一个方向上运输精子，而是施加向心力，通过鞭子般的跳动与方向的不断变化，产生湍流，保持不动的精子在管腔内悬浮液。两个miRNA簇的基因切除（miR-34 B/c和-449 a/B/c）由于许多基因的失调而导致小鼠输出小管中多纤毛发生失败，并且该小鼠模型使我们能够证明输出小管运动纤毛的丧失导致精子聚集和凝集、管腔阻塞和精子肉芽肿，这反过来，导致睾丸的反压性萎缩，最终导致男性不育。
Significance Motile cilia are found lining the respiratory and reproductive systems, as well as the brain and spinal column, and the coordinated beat moves fluids over the luminal surfaces. Disruptions of ciliary structure or beat patterns have been shown to be involved in numerous diseases called ciliopathies. For many years, it has been proposed that the ciliary beat in the male reproductive system propels sperm from testis into the epididymis via tiny efferent ductules. Here, we show that motile cilia lining the efferent ductules do not directly propel sperm, but rather serve as agitators, generating vigorous fluidic turbulence, to maintain suspension of sperm within the intraluminal fluid, thus ensuring an equilibrium in fluid reabsorption by the nonciliated cells. Cilia are cell-surface, microtubule-based organelles that project into extracellular space. Motile cilia are conserved throughout eukaryotes, and their beat induces the flow of fluid, relative to cell surfaces. In mammals, the coordinated beat of motile cilia provides highly specialized functions associated with the movement of luminal contents, as seen with metachronal waves transporting mucus in the respiratory tract. Motile cilia are also present in the male and female reproductive tracts. In the female, wave-like motions of oviductal cilia transport oocytes and embryos toward the uterus. A similar function has been assumed for motile cilia in efferent ductules of the male—i.e., to transport immotile sperm from rete testis into the epididymis. However, we report here that efferent ductal cilia in the male do not display a uniform wave-like beat to transport sperm solely in one direction, but rather exert a centripetal force on luminal fluids through whip-like beating with continual changes in direction, generating turbulence, which maintains immotile spermatozoa in suspension within the lumen. Genetic ablation of two miRNA clusters (miR-34b/c and -449a/b/c) led to failure in multiciliogenesis in murine efferent ductules due to dysregulation of numerous genes, and this mouse model allowed us to demonstrate that loss of efferent duct motile cilia causes sperm aggregation and agglutination, luminal obstruction, and sperm granulomas, which, in turn, induce back-pressure atrophy of the testis and ultimately male infertility.
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DOI：
10.1677/joe.0.0230285
发表时间：
1961-12
期刊：
The Journal of endocrinology
影响因子：
--
作者：
A. Wallace;K. Ferguson
通讯作者：
A. Wallace;K. Ferguson
DOI：
10.4103/0970-2113.56352
发表时间：
2009-10
期刊：
Lung India : official organ of Indian Chest Society
影响因子：
--
作者：
Dixit R;Dixit K;Jindal S;Shah KV
通讯作者：
Shah KV
影响因子：
7.2
作者：
Braun DA;Hildebrandt F
通讯作者：
Hildebrandt F
DOI：
10.1097/00000478-200404000-00011
发表时间：
2004-04
期刊：
The American Journal of Surgical Pathology
影响因子：
--
作者：
M. Nistal;Miguel Ángel García-Cabezas;J. Regadera;M. C. Castillo
通讯作者：
M. Nistal;Miguel Ángel García-Cabezas;J. Regadera;M. C. Castillo
影响因子：
--
作者：
H. Winet
通讯作者：
H. Winet