DNA integrity is compromised in protamine-deficient human sperm

DNA integrity is compromised in protamine-deficient human sperm
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DOI:
10.2164/jandrol.05063
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发表时间:
2005-11-01
影响因子:
--
通讯作者:
Carrell, DT
Carrell, DT
中科院分区:
其他
文献类型:
--
作者:
Aoki, VW;Moskovtsev, SI;Carrell, DT

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本研究的目的是检查人类精子中 DNA 完整性和鱼精蛋白之间的关系。机构审查委员会批准的一项研究纳入了一百四十九名男性不育患者。使用 DNA 完整性测定评估精子的 DNA 碎片,该测试相当于精子染色质结构测定 (SCSA)。此外,还提取了核蛋白,并评估了鱼精蛋白 1/鱼精蛋白 2 比率 (P1/P2)、鱼精蛋白 1 (P1)、鱼精蛋白 2 (P2) 和鱼精蛋白总浓度。我们确定了 37 名 P1/P2 比值异常低的患者、99 名 P1/P2 比值正常的患者和 13 名 P1/P2 比值异常高的患者。与 P1/P2 比率正常和高的患者(分别为 26.7 +/- 1.9 和 23.8 +/- 3.2;P < .05)相比,P1/P2 比率低的患者 (37.1 +/- 6.02) 的 DNA 碎片显着升高,并且与 P1/P2 比率 (R-3 -0.18,P < .05)、P1 浓度 (R-3) 呈负相关。 -0.29,P < .001)、P2 浓度 (R-3 -0.24,P < .005) 和总谷醇溶蛋白浓度 (R-3 -0.28,P < .001)。此外,chi(2) 分析显示,P1 或 P2 水平降低的患者中,显着 DNA 断裂的发生率显着增加。本研究首次报道人类精子中谷醇溶蛋白含量与DNA断裂显着相关。特别是,精子 P1 和 P2 浓度与 DNA 碎片呈负相关,表明谷醇溶蛋白对精子 DNA 损伤具有保护作用。鉴于最近的研究强调了精子 DNA 损伤对 ART 结果的负面影响,这些发现表明人类精子谷醇溶蛋白水平可能具有临床意义。
The objective of this study was to examine the relationship between DNA integrity and protamines in human sperm. One hundred forty-nine male infertility patients were included in an Institutional Review Board-approved study. Sperm were evaluated for DNA fragmentation using the DNA Integrity Assay, a test equivalent to the sperm chromatin structure assay (SCSA). Additionally, nuclear proteins were extracted and the protamine-1/protamine-2 ratio (P1/P2), protamine-1 (P1), protamine-2 (P2), and total protamine concentrations were evaluated. We identified 37 patients with abnormally low P1/P2 ratios, 99 patients with normal P1/P2 ratios, and 13 patients with abnormally high P1/P2 ratios. DNA fragmentation was significantly elevated in patients with low P1/P2 ratios (37.1 +/- 6.02) vs those with normal and high P1/P2 ratios (26.7 +/- 1.9 and 23.8 +/- 3.2, respectively; P < .05) and was inversely correlated with the P1/P2 ratio (R-3 -0.18, P < .05), P1 concentration (R-3 -0.29, P < .001), P2 concentration (R-3 -0.24, P < .005), and total prolamine concentration (R-3 -0.28, P < .001). Furthermore, chi(2) analysis revealed a significant increase in the incidence of marked DNA fragmentation in patients with diminished levels of either P1 or P2. The present study is the first to report that human sperm prolamine content is significantly related to DNA fragmentation. In particular, sperm P1 and P2 concentrations inversely correlate with DNA fragmentation, indicating a protective role of the prolamines against sperm DNA damage. In light of recent studies highlighting the negative effect of sperm DNA damage on ART outcomes, these findings indicate a possible clinical significance for human sperm prolamine levels.