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

Golgi-associated PDZ- and coil -coil motif-containing protein)^<-/->小鼠不育，表现为球精症、盘绕尾巴和层状线粒体鞘。定量研究了精子的透射电子显微镜（TEM）图像，以分析附睾通过过程中的紊乱过程。用透射电镜和免疫荧光显微镜观察维持直尾和正常线粒体鞘的因素。附睾头近端精子尾部保持正常外观。尾部解体开始于附睾头近端和中端之间，后端为主要部位。尾巴向上移动，穿过有缺陷的后环，不同程度地缠绕在细胞核周围。尾盘绕发生在附睾头，提示这是由细胞质液滴迁移引起的。线粒体粘附蛋白SPATA19/spergen-1主要分布在层状线粒体上，而线粒体被囊的主要成分GPX4/ PHGPx则不均匀分布在层状线粒体上。根据这些发现，我们推测GPX4对于维持正常的鞘结构是必要的，而SPATA19阻止线粒体的分散，导致在Gopc^<-/->精子中形成分层的线粒体鞘。附睾上皮结构正常，LRP8/apoER2表达正常，提示尾巴异常与精子内在因素有关。在附睾成熟过程中，有三种细胞结构是维持尾直的必要因素：1)完整的后环以防止尾侵犯头腔；2)连接片与着床窝的稳定附着；3)由SPATA19支撑并提供充足且正态分布的GPX4的正常线粒体鞘。

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.