Motility of efferent duct cilia aids passage of sperm cells through the male reproductive system.
Motility of efferent duct cilia aids passage of sperm cells through the male reproductive system.
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DOI：
10.1093/molehr/gaab009
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发表时间：
2021-02-27
影响因子：
4
通讯作者：
Omran H
中科院分区：
文献类型：
--
作者：
Aprea I;Nöthe-Menchen T;Dougherty GW;Raidt J;Loges NT;Kaiser T;Wallmeier J;Olbrich H;Strünker T;Kliesch S;Pennekamp P;Omran H
活动纤毛排列在哺乳动物雄性生殖道的输出管上。最近的几项小鼠研究表明，输出管中多个运动纤毛的产生减少与阻塞性少精子症和生育问题有关。然而，输出管纤毛运动障碍对男性不育的唯一影响迄今尚未在小鼠或人类中进行研究。使用视频显微镜，组织学和超微结构分析，我们研究了雄性生殖道的小鼠缺乏轴丝马达蛋白DNAH5：这种缺陷专门破坏外动力蛋白臂（ODA）组成的运动纤毛，但不ODA组成和精子鞭毛的活力。这些小鼠具有缺乏ODA的不动传出导管纤毛，ODA是纤毛搏动产生所必需的。此外，它们显示精子在输出管中积聚。值得注意的是，这些雄性动物精子的超微结构和活力不受影响。同样，具有功能丧失的DNAH5突变的人类个体表现为射精中精子计数减少（少精子症）和附睾头缩短，但精子活力正常，类似于DNAH5缺陷小鼠。这项翻译研究的结果表明，在小鼠和男性，输出管纤毛运动是重要的男性生殖健康和揭示了一种新的病理机制不同的原发性缺陷的精子活力（弱精子症）。如果未来的工作可以确定DNA H5以外的环境因素或基因缺陷导致输出管纤毛运动障碍，这将有助于解开少精子症的其他原因，并可能影响未来的遗传和生育咨询以及ART的实践。
Motile cilia line the efferent ducts of the mammalian male reproductive tract. Several recent mouse studies have demonstrated that a reduced generation of multiple motile cilia in efferent ducts is associated with obstructive oligozoospermia and fertility issues. However, the sole impact of efferent duct cilia dysmotility on male infertility has not been studied so far either in mice or human. Using video microscopy, histological- and ultrastructural analyses, we examined male reproductive tracts of mice deficient for the axonemal motor protein DNAH5: this defect exclusively disrupts the outer dynein arm (ODA) composition of motile cilia but not the ODA composition and motility of sperm flagella. These mice have immotile efferent duct cilia that lack ODAs, which are essential for ciliary beat generation. Furthermore, they show accumulation of sperm in the efferent duct. Notably, the ultrastructure and motility of sperm from these males are unaffected. Likewise, human individuals with loss-of-function DNAH5 mutations present with reduced sperm count in the ejaculate (oligozoospermia) and dilatations of the epididymal head but normal sperm motility, similar to DNAH5 deficient mice. The findings of this translational study demonstrate, in both mice and men, that efferent duct ciliary motility is important for male reproductive fitness and uncovers a novel pathomechanism distinct from primary defects of sperm motility (asthenozoospermia). If future work can identify environmental factors or defects in genes other than DNAH5 that cause efferent duct cilia dysmotility, this will help unravel other causes of oligozoospermia and may influence future practices in genetic and fertility counseling as well as ART.
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影响因子：
3.5
作者：
Ibañez-Tallon, I;Gorokhova, S;Heintz, N
通讯作者：
Heintz, N
影响因子：
10.7
作者：
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通讯作者：
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9.8
作者：
Hoeben, Inga M.;Hjeij, Rim;Omran, Heymut
通讯作者：
Omran, Heymut
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3.7
作者：
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通讯作者：
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影响因子：
9.8
作者：
Loges, Niki Tomas;Olbrich, Heike;Omran, Heymut
通讯作者：
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