Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China.
J Proteome Res. 2010 Mar 5;9(3):1246-56. doi: 10.1021/pr900735k.
Spermiogenesis is a unique process in mammals during which haploid round spermatids mature into spermatozoa in the testis. Its successful completion is necessary for fertilization and its malfunction is an important cause of male infertility. Here, we report the high-confidence identification of 2116 proteins in mouse haploid germ cells undergoing spermiogenesis: 299 of these were testis-specific and 155 were novel. Analysis of these proteins showed many proteins possibly functioning in unique processes of spermiogenesis. Of the 84 proteins annotated to be involved in vesicle-related events, VAMP4 was shown to be important for acrosome biogenesis by in vivo knockdown experiments. Knockdown of VAMP4 caused defects of acrosomal vesicle fusion and significantly increased head abnormalities in spermatids from testis and sperm from the cauda epididymis. Analysis of chromosomal distribution of the haploid genes showed underrepresentation on the X chromosome and overrepresentation on chromosome 11, which were due to meiotic sex chromosome inactivation and expansion of testis-expressed gene families, respectively. Comparison with transcriptional data showed translational regulation during spermiogenesis. This characterization of proteins involved in spermiogenesis provides an inventory of proteins useful for understanding the mechanisms of male infertility and may provide candidates for drug targets for male contraception and male infertility.
精子发生是哺乳动物中一个独特的过程，在此过程中，单倍体圆形精母细胞在睾丸中成熟为精子。它的成功完成对于受精是必要的，其功能障碍是男性不育的一个重要原因。在这里，我们报告了在精子发生过程中鉴定出的 2116 种高可信度的小鼠单倍体生殖细胞中的蛋白质：其中 299 种是睾丸特异性的，155 种是新的。对这些蛋白质的分析表明，许多蛋白质可能在精子发生的独特过程中发挥作用。在注释为参与囊泡相关事件的 84 种蛋白质中，VAMP4 通过体内敲低实验被证明对顶体生物发生很重要。VAMP4 的敲低导致顶体囊泡融合缺陷，并显著增加了睾丸精子和附睾尾部精子中精母细胞的头部异常。单倍体基因的染色体分布分析显示，X 染色体上的代表性不足和 11 号染色体上的代表性过多，这分别是由于减数分裂性染色体失活和睾丸表达基因家族的扩张所致。与转录数据的比较表明，在精子发生过程中存在翻译调控。这些参与精子发生的蛋白质的特征提供了一个有用的蛋白质清单，有助于理解男性不育的机制，并可能为男性避孕和男性不育的药物靶点提供候选物。
