Department of Microbiology and Immunology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA.
PLoS One. 2013 Jul 30;8(7):e70470. doi: 10.1371/journal.pone.0070470. Print 2013.
A number of laboratory tests have been developed to determine properties of spermatozoa quality but few have been adopted into routine clinical use in place of the WHO semen analysis. We investigated whether Atp6v0a2 (a2 isoform of vacuolar ATPase) is associated with abnormal semen quality and changes in chemokine-cytokine profiles in infertile men.
Semen samples were collected from 35 healthy donors and 35 infertile men at the Andrology laboratory from August 2011 to June 2012. The levels of Atp6v0a2 mRNA and protein, and its localization in spermatozoa were determined. a2NTD (the N-terminal portion of Atp6v0a2) and secreted chemokine-cytokine profiles in seminal fluid were measured.
Atp6v0a2 protein (P<0.05) and mRNA (P<0.05) in spermatozoa from infertile men were significantly lower than those from fertile men. Fluorescent microscopy revealed that Atp6v0a2 is mainly expressed in the acrosomal region. Infertile men's seminal fluid had significantly lower G-CSF (P<0.01), GM-CSF (P<0.01), MCP-1 (P<0.05), MIP-1α (P<0.01) and TGF-β1 (P<0.01) levels when compared to the seminal fluid from fertile men. Seminal fluid a2NTD levels were significantly correlated with G-CSF (P<0.01), GM-CSF (P<0.01), MCP-1 (P<0.05), MIP-1α (P<0.01) and TGF-β1 (P<0.01) which are key molecules during the onset of pregnancy.
These results suggested that a critical level of Atp6v0a2 is required for the fertile spermatozoa and its decreased level in spermatozoa could be used to predict male infertility. This study provides a possibility that Atp6v0a2 could be potentially used as a diagnostic marker for the evaluation of male infertility.
已经开发出许多实验室测试来确定精子质量的特性，但很少有测试能够替代世界卫生组织的精液分析而被常规临床采用。我们研究了三磷酸腺苷酶（ATP 酶）V0 亚基 A2（ATP6V0A2，也称为 vacuolar ATPase 的 a2 同工型）是否与不育男性的精液质量异常和趋化因子-细胞因子谱的变化有关。
2011 年 8 月至 2012 年 6 月，我们从男科实验室收集了 35 名健康供体和 35 名不育男性的精液样本。确定了精子中 ATP6V0A2mRNA 和蛋白质的水平及其定位。测量了 a2NTD（ATP6V0A2 的 N 端部分）和精液中分泌的趋化因子-细胞因子谱。
与正常生育男性相比，不育男性精子中的 ATP6V0A2 蛋白（P<0.05）和 mRNA（P<0.05）显著降低。荧光显微镜显示，ATP6V0A2 主要表达在顶体区域。与正常生育男性相比，不育男性的精液中 G-CSF（P<0.01）、GM-CSF（P<0.01）、MCP-1（P<0.05）、MIP-1α（P<0.01）和 TGF-β1（P<0.01）水平显著降低。精液 a2NTD 水平与 G-CSF（P<0.01）、GM-CSF（P<0.01）、MCP-1（P<0.05）、MIP-1α（P<0.01）和 TGF-β1（P<0.01）显著相关，这些都是妊娠开始时的关键分子。
这些结果表明，ATP6V0A2 的临界水平对于正常生育的精子是必需的，精子中该水平的降低可用于预测男性不育。本研究提供了一种可能性，即 ATP6V0A2 可潜在用作评估男性不育的诊断标志物。
