记者从烟台获悉,由山东省干细胞工程技术研究中心、烟台毓璜顶医院、烟台大学李建远教授率领的研究团队,经过十年的潜心研究,在人类精子成熟相关蛋白研究中取得重大突破,研究成果连续被美国国际著名学术期刊MCP《分子与细胞蛋白质组学》2010年11期和12月22日在线发表。这标志着我国人类精子成熟相关研究进入了国际原创领先阶段。
据介绍,人类精子成熟是男性生殖调控的重要环节。精子在睾丸中产生,通过附睾管腔微环境与附睾分泌蛋白相互作用发育成熟,为随后的受精奠定基础。精子成熟障碍是引起男性不育的主要原因之一, 因此, 研究精子成熟相关蛋白有助于提高临床不育的分子诊断及治疗水平。此外, 干扰精子成熟,还可以调控生殖有效避孕。
李教授的研究团队,以源头创新为起点,采用系统工程化分子生物学研究技术手段,在成功解析了正常人附睾基因表达谱的基础上,又解析了人类附睾、睾丸蛋白表达谱,附睾管腔液分泌型蛋白谱,并建立了相应1030种蛋白抗体库,鉴定发现附睾和睾丸表达的精子定位蛋白317种(包含了人附睾分泌精子结合蛋白家族),对其进行了科学系统的分类编号与命名,并注册于国际人类组织基因库(GenBank)。这对于人们进一步了解精子上的定位蛋白的潜在功能提供了基础。该团队通过功能研究发现了与精子运动、穿卵、获能、抗氧化和免疫防御等功能有关的重要靶蛋白。其所建立的人类精子成熟相关蛋白生物信息数据库,通过网络对国际开放,实现了信息资源共享。
据悉,山东省科技厅于2009年12月20日组织国内著名专家评审委员会对该成果进行了鉴定。评审委员会认为此成果具有原创性、先进性、科学性和实用性,达到国际领先水平。(生物谷Bioon.com)
研究文章出处:
Molecular & Cellular Proteomics doi: 10.1074/mcp.M110.004630
Mapping of the human testicular proteome and its relationship with that of the epididymis and spermatozoa
JianYuan Li1,*, FuJun Liu1, Xin Liu1, Juan Liu1, Peng Zhu1, FengChun Wan2, ShaoHua Jin1, Ning Li1, Jie Liu1 and HaiYan Wang1
Abstract
The testis produces male gametes in the germinal epithelium through the development of spermatogonia and spermatocytes into spermatids and immature spermatozoa with the support of Sertoli cells. The flow of sperm into the epididymis is aided by testicular secretions. In the epididymal lumen, spermatozoa and testicular secretions combine with epididymal secretions that promote sperm maturation and storage. We refer to the combined secretions in the epididymis as the sperm-milieu. With 2D-PAGE MALDI-TOF/MS analysis of healthy testes from fertile accident victims, 725 unique proteins were identified from 1920 2D-gel spots, and a corresponding antibody library was established. This revealed the presence of 240 proteins in the sperm-milieu by Western blotting and the localisation of 167 proteins in mature spermatozoa by immuno-cytochemistry. These proteins, and those from the epididymal proteome (Li et al. 2010), form the proteomes of the sperm-milieu and the spermatozoa, comprising 525 and 319 proteins, respectively. Individual mapping of the 319 sperm-located proteins to various testicular cell types by immunohistochemistry suggested that 47% were intrinsic sperm proteins (from their presence in spermatids) and 23% were extrinsic sperm proteins, originating from the epididymis and acquired during maturation (from their absence from the germinal epithelium and presence in the epididymal tissue and sperm-milieu). Whereas 408 of 525 proteins in the sperm-milieu proteome were previously identified as abundant epididymal proteins, the remaining 22%, detected by the use of new testicular antibodies, were more likely to be minor proteins common to the testicular proteome, rather than proteins of testicular origin added to spermatozoa during maturation in the epididymis. The characterization of the sperm-milieu proteome and testicular mapping of the sperm-located proteins presented here provide the molecular basis for further studies on the production and maturation of spermatozoa. This could be the basis of development of diagnostic markers and therapeutic targets for infertility or male contraception.