Disintegration of spermatozoa : Molecular mechanism of coiled tail and round-head formation

Gopc(高尔基相关的PDZ和螺旋卷曲基序包含蛋白)^&lt；-/-&gt；小鼠是不育的，表现为球精子症、卷曲的尾巴和分层的线粒体鞘。对精子的透射电子显微镜图像进行了定量研究，以分析精子在附睾道过程中的解体过程。用透射电子显微镜和免疫荧光显微镜研究了保持直尾和正常线粒体鞘的因素。附睾头近端的精子尾巴保持了正常的外观。尾部解体始于附睾头近端和附睾头中段，后者是尾部解体的主要部位。尾巴向上移动穿过有缺陷的后环，并不同程度地盘绕在细胞核周围。尾巴卷曲发生在附睾头，提示它是由细胞质液滴迁移触发的。候选线粒体黏附蛋白SPATA19/SPERGEN-1保留在复层线粒体上，而线粒体被膜的主要成分Gpx4/PHGPx分布不均。根据这些发现，我们推测Gpx4是维持正常鞘结构所必需的，而SPATA19阻止了线粒体的扩散，导致了Gopc^&lt；-/-&gt；精子中线粒体鞘的分层形成。附睾上皮细胞结构正常，LRP8/ApoER2表达正常，提示尾部异常是由精子因素引起的。在附睾成熟过程中，有三种细胞结构可作为维持直尾的必要条件：1)一个完整的后环，以防止尾部侵入头部；2)连接件稳定地附着在植入窝上；3)由SPATA19支持的正常线粒体鞘，并提供充足且正常分布的Gpx4。

Gopc (Golgi-associated PDZ- and coiled-coil motif-containing protein)^<-/-> mice are infertile, showing globozoospermia, coiled tails and a stratified mitochondrial sheath. Transmission electron microscope (TEM) images of the spermatozoa were studied quantitatively to analyze disorganization processes during epididymal passage. Factors maintaining straight tail and normal mitochondrial sheath were also studied by TEM and immunoflorescent microscopy.Sperm tails retained a normal appearance in the proximal caput epididymidis. Tail disorganization started between the proximal and the middle caput epididymidis, and the latter is the major site for it. The tail moved up through the defective posterior ring and coiled around the nucleus to various degrees. Tail coiling occurred in the caput epididymidis suggesting it was triggered by cytoplasmic droplet migration. SPATA19/spergen-1, a candidate mitochondrial adhesion protein, remained on the stratified mitochondria, while GPX4/ PHGPx, a major element of the mitochondrial capsule, was unevenly distributed on them. From these findings, we speculate GPX4 is necessary to maintain normal sheath structure, and SPATA19 prevents dispersal of mitochondria, resulting in a stratified mitochondrial sheath formation in Gopc^<-/-> spermatozoa. The epididymal epithelium was normal in structure and LRP8/apoER2 expression suggesting that tail abnormality is due to intrinsic sperm factors.Three cell-structures can be condisered as requisite factors for maintaining a straight tail during epididymal maturation: 1) a complete posterior ring to prevent invasion of the tail into the head compartment, 2) stable attachment of the connecting piece to the implantation fossa, 3) a normal mitochondrial sheath supported by SPATA19 and supplied with sufficient and normally distributed GPX4.