Infertile spermatozoa of c-ros tyrosine kinase receptor knockout mice show flagellar angulation and maturational defects in cell volume regulatory mechanisms
Infertile spermatozoa of c-ros tyrosine kinase receptor knockout mice show flagellar angulation and maturational defects in cell volume regulatory mechanisms
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DOI：
10.1095/biolreprod61.4.1062
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发表时间：
1999-10-01
影响因子：
3.6
通讯作者：
Cooper, TG
中科院分区：
文献类型：
--
作者：
Yeung, CH;Sonnenberg-Riethmacher, E;Cooper, TG
纯合子c-ros基因敲除的雄性小鼠，缺乏青春期前附睾起始段的分化是健康的，但不育，尽管正常的精子生产和交配。对附睾中成熟精子的运动力进行详细的计算机分析，发现只有轻微的缺陷。然而，大多数从附睾尾释放的能动成熟精子显示出不同程度的鞭毛成角，不能通过提高细胞外渗透压来纠正。附睾尾液渗透压的测量结果与野生型无差异。在野生型小鼠中的研究表明，在孵化过程中，活动精子保持直鞭毛的能力发生成熟变化，但通过体积敏感性离子通道阻断剂奎宁、5-硝基-2-（3-苯丙氨基）-苯甲酸和氯化钡或暴露于低渗介质，可诱导尾部精子成角。鞭毛成角，在野生型或内在的敲除诱导，解除后，通过Triton X-100的脱膜，证实这是一种细胞肿胀现象。未成熟的野生型精子和成熟的敲除精子对通道阻滞剂缺乏反应，这表明成熟后通常会出现体积调节机制，而敲除动物的精子中存在缺陷。由此产生的鞭毛成角可能是导致交配雌性输卵管中精子数量减少和体内受精失败的原因。
Homozygous c-ros knockout male mice that lack prepubertal differentiation of the epididymal initial segment are healthy but sterile, despite normal sperm production and mating. Detailed computerized analysis of the motility of spermatozoa maturing in the epididymis revealed only minor defects. However, the majority of motile mature sperm released from the cauda epididymidis showed various extents of flagellar angulation that could not be corrected by raising extracellular osmolality. Measurement of the osmolality of cauda epididymal fluid showed no difference from the wild type. Studies in wild-type mice indicated a maturational change in the ability of motile sperm to maintain straight flagella during incubation, but angulation was induced in cauda sperm by the volume-sensitive ion channel blockers quinine, 5-nitro-2-(3-phenylpropylamino)-benzoic acid and BaCl2, or by exposure to hypotonic media. Flagellar angulation, induced in the wild type or intrinsic to the knockout, was relieved upon demembranation by Triton X-100, confirming that it was a cell swelling phenomenon. A lack of response of immature wild-type sperm and mature knockout sperm to the channel blockers suggests that there is normally a development of the volume regulatory mechanisms upon maturation that is defective in sperm from the knockout animal. The resultant flagellar angulation may account for the reduction in sperm numbers in the oviduct of mated females and the failure to fertilize in vivo.