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氧化应激与凋亡增加相关,从而导致男性因素不育患者的精子DNA损伤。

Oxidative stress is associated with increased apoptosis leading to spermatozoa DNA damage in patients with male factor infertility.

作者信息

Wang Xia, Sharma Rakesh K, Sikka Suresh C, Thomas Anthony J, Falcone Tommaso, Agarwal Ashok

机构信息

Center for Advanced Research in Human Reproduction, Infertility, and Sexual Function, Department of Obsterics and Gynecology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

出版信息

Fertil Steril. 2003 Sep;80(3):531-5. doi: 10.1016/s0015-0282(03)00756-8.

DOI:10.1016/s0015-0282(03)00756-8
PMID:12969693
Abstract

OBJECTIVE

To evaluate ejaculated spermatozoa from patients with male factor infertility for the role of cytochrome c and caspases 9 and 3 (the proteins known to mediate apoptosis) and to examine association between semen quality and apoptosis in the presence of oxidative stress.

DESIGN

Prospective study.

SETTING

Male infertility clinic at a tertiary health care center.

PATIENT(S): Semen specimens from 35 patients with idiopathic infertility and 8 normal healthy donors.

MAIN OUTCOME MEASURE(S): Levels of ROS, cytochrome c, and caspases 9 and 3 and semen variables.

RESULT(S): Compared with normal donors, infertile patients had significantly higher levels (expressed as median [25th and 75th percentiles]) of ROS (4.15 x 10(6) counted photons per minute [cpm] [0.26, 40.16 x 10(6) cpm] vs. 0.06 x 10(6) cpm [0.02, 0.29 x 10(6) cpm]; P<.01), cytochrome c (2.78 [2.21, 43.65 vs. 1.5 [1.25, 2.2]; P<.01)], caspase 9 (2.52 [0.9, 4.28] vs. 6 [4.85, 7.63]; P<.006), and caspase 3 (0.56 [0.32, 1.02] vs. 1.69 [1.66, 2.67]; P<.01). Semen variables (motility, concentration, and morphology) were negatively correlated with caspase 9 and 3 (P<.05). Reactive oxygen species was positively correlated with cytochrome c (r=.43; P<.03), caspase 9 (r=.56; P<.001), and caspase 3 (r=.65;P<.01).

CONCLUSION(S): Infertile men have decreased sperm variables induced by higher ROS levels in semen. A positive relationship exists between increased sperm damage by ROS and higher levels of cytochrome c and caspases 9 and 3, which indicate positive apoptosis in patients with male factor infertility.

摘要

目的

评估男性因素不育患者射出的精子中细胞色素c以及半胱天冬酶9和3(已知介导细胞凋亡的蛋白质)的作用,并研究在氧化应激存在的情况下精液质量与细胞凋亡之间的关联。

设计

前瞻性研究。

地点

一家三级医疗保健中心的男性不育诊所。

患者

35例特发性不育患者和8名正常健康供者的精液标本。

主要观察指标

活性氧(ROS)、细胞色素c、半胱天冬酶9和3的水平以及精液变量。

结果

与正常供者相比,不育患者的ROS水平(以中位数[第25和第75百分位数]表示)显著更高(4.15×10⁶计数光子每分钟[cpm][0.26,40.16×10⁶ cpm] 对比0.06×10⁶ cpm [0.02,0.29×10⁶ cpm];P<0.01)、细胞色素c(2.78 [2.21,43.65] 对比1.5 [1.25,2.2];P<0.01)、半胱天冬酶9(2.52 [0.9,4.28] 对比6 [4.85,7.63];P<0.006)以及半胱天冬酶3(0.56 [0.32,1.02] 对比1.69 [1.66,2.67];P<0.01)。精液变量(活力、浓度和形态)与半胱天冬酶9和3呈负相关(P<0.05)。活性氧与细胞色素c呈正相关(r = 0.43;P<0.03)、与半胱天冬酶9呈正相关(r = 0.56;P<0.001)以及与半胱天冬酶3呈正相关(r = 0.65;P<0.01)。

结论

不育男性精液中较高的ROS水平导致精子变量降低。ROS导致的精子损伤增加与细胞色素c以及半胱天冬酶9和3的较高水平之间存在正相关关系,这表明男性因素不育患者存在阳性细胞凋亡。

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