Sutovsky Peter, Hauser Russ, Sutovsky Miriam
Department of Animal Science, University of Missouri-Columbia, 65211-5300, USA.
Hum Reprod. 2004 Mar;19(3):628-38. doi: 10.1093/humrep/deh131.
Ubiquitin, a house-keeping protein that marks other proteins for proteasomal degradation, tags defective sperm during epididymal passage. To establish ubiquitin as a biomarker of human infertility, the present study examines the relationships between sperm ubiquitin content and clinical semen parameters among men from an infertility clinic population with varied aetiologies.
Anti-ubiquitin immunoreactivity was measured by flow cytometric sperm-ubiquitin tag immunoassay (SUTI) in sperm samples of 28 infertility patients and 15 fertile donors. Semen analyses were performed by computer-assisted semen analysis and World Health Organization morphology.
Median values of ubiquitin-induced fluorescence had a strong negative correlation with sperm count (r = -0.63, P = 0.0003) and a positive correlation with % abnormal morphology (r = 0.55, P = 0.01). Infertility patients (n = 28) had significantly higher levels of sperm ubiquitin. Out of 28 patients, six reported possible occupational exposures to solvents, three were current smokers and six were ex-smokers. Within the patient group, men with known male factor infertility, those with self-reported occupational exposure to solvents and current smokers had the highest sperm ubiquitin levels. When men with jobs involving potential occupational exposure to solvents were combined with current smokers, the highest correlations were found between sperm ubiquitin and motility (r = -0.74), count (r = -0.82) and % sperm abnormalities (r = 0.73).
Increased sperm ubiquitin was inversely associated with sperm count, motility and % normal morphology, supporting the use of ubiquitin as a biomarker of human semen quality. SUTI assay confirmed poor semen quality in all men with poor clinical semen parameters, but also was high in some patients with seemingly good clinical semen parameters. Occupational exposure to solvents and smoking may have contributed to high levels of sperm ubiquitin in some of these patients.
泛素是一种管家蛋白,可标记其他蛋白以便蛋白酶体降解,在精子通过附睾的过程中标记有缺陷的精子。为了将泛素确立为人类不育的生物标志物,本研究调查了不育门诊不同病因男性群体中精子泛素含量与临床精液参数之间的关系。
采用流式细胞术精子泛素标记免疫测定法(SUTI)检测28例不育患者和15例生育力正常供者的精子样本中的抗泛素免疫反应性。通过计算机辅助精液分析和世界卫生组织形态学标准进行精液分析。
泛素诱导的荧光中位数与精子计数呈强负相关(r = -0.63,P = 0.0003),与形态异常百分比呈正相关(r = 0.55,P = 0.01)。不育患者(n = 28)的精子泛素水平显著更高。28例患者中,6例报告可能职业接触过溶剂,3例为现吸烟者,6例为既往吸烟者。在患者组中,已知男性因素不育的男性、自我报告职业接触过溶剂的男性和现吸烟者的精子泛素水平最高。当将有潜在职业接触溶剂工作的男性与现吸烟者合并时,发现精子泛素与活力(r = -0.74)、计数(r = -0.82)和精子异常百分比(r = 0.73)之间的相关性最高。
精子泛素增加与精子计数、活力和正常形态百分比呈负相关,支持将泛素用作人类精液质量的生物标志物。SUTI测定法证实所有临床精液参数差的男性精液质量差,但在一些临床精液参数看似良好的患者中该指标也较高。职业接触溶剂和吸烟可能导致了其中一些患者精子泛素水平升高。