A critical role of solute carrier 22a14 in sperm motility and male fertility in mice.
A critical role of solute carrier 22a14 in sperm motility and male fertility in mice.
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DOI：
10.1038/srep36468
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发表时间：
2016-11-04
影响因子：
4.6
通讯作者：
Yogo K
中科院分区：
文献类型：
--
作者：
Maruyama SY;Ito M;Ikami Y;Okitsu Y;Ito C;Toshimori K;Fujii W;Yogo K
我们以前确定溶质载体22 a14（Slc 22 a14）作为精子发生相关的跨膜蛋白在小鼠。虽然Slc 22 a14是有机阴离子/阳离子转运蛋白家族的成员，但其表达谱和生理作用尚未阐明。在这里，我们表明Slc 22 a14对小鼠的精子活力和雄性生育力至关重要。Slc 22 a14在雄性生殖细胞中特异性表达，缺乏Slc 22 a14基因的小鼠表现出严重的雄性不育。虽然精子的整体分化是正常的，但Slc 22 a14 −/−尾部附睾精子的活动力降低，鞭毛弯曲异常。此外，Slc 22 a14 −/−精子迁移到雌性生殖道并使卵母细胞受精的能力也受到损害。由于渗透性攻击或膜透化处理减轻了尾部异常，因此认为异常鞭毛弯曲部分由渗透性细胞肿胀引起。此外，我们发现Slc 22 a14 −/−精子细胞的结构异常：环，一个在中间片-主片连接处的环状结构，是混乱的，和septin 4的表达和定位，一个环的组成蛋白是必不可少的环的形成，也受到损害。综上所述，我们的研究结果表明，Slc 22 a14在小鼠精子的正常鞭毛结构，运动性和生育力中起着关键作用。
We previously identified solute carrier 22a14 (Slc22a14) as a spermatogenesis-associated transmembrane protein in mice. Although Slc22a14 is a member of the organic anion/cation transporter family, its expression profile and physiological role have not been elucidated. Here, we show that Slc22a14 is crucial for sperm motility and male fertility in mice. Slc22a14 is expressed specifically in male germ cells, and mice lacking the Slc22a14 gene show severe male infertility. Although the overall differentiation of sperm was normal, Slc22a14−/− cauda epididymal spermatozoa showed reduced motility with abnormal flagellar bending. Further, the ability to migrate into the female reproductive tract and fertilise the oocyte were also impaired in Slc22a14−/− spermatozoa. The abnormal flagellar bending was thought to be partly caused by osmotic cell swelling since osmotic challenge or membrane permeabilisation treatment alleviated the tail abnormality. In addition, we found structural abnormalities in Slc22a14−/− sperm cells: the annulus, a ring-like structure at the mid-piece–principal piece junction, was disorganised, and expression and localisation of septin 4, an annulus component protein that is essential for the annulus formation, was also impaired. Taken together, our results demonstrated that Slc22a14 plays a pivotal role in normal flagellar structure, motility and fertility in mouse spermatozoa.
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影响因子：
11.8
作者：
Kissel, H;Georgescu, MM;Steller, H
通讯作者：
Steller, H
影响因子：
64.8
作者：
Enomoto, A;Kimura, H;Endou, H
通讯作者：
Endou, H
影响因子：
2.2
作者：
Haan, Claude;Behrmann, Iris
通讯作者：
Behrmann, Iris
DOI：
10.1038/nrd4626
发表时间：
2015-08
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Lin L;Yee SW;Kim RB;Giacomini KM
通讯作者：
Giacomini KM
DOI：
10.1073/pnas.1016902108
发表时间：
2011-01-11
影响因子：
11.1
作者：
Jimenez, Tamara;McDermott, Jeffrey P.;Blanco, Gustavo
通讯作者：
Blanco, Gustavo