Proteomic signatures of infertile men with clinical varicocele and their validation studies reveal mitochondrial dysfunction leading to infertility.
Proteomic signatures of infertile men with clinical varicocele and their validation studies reveal mitochondrial dysfunction leading to infertility.
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DOI：
10.4103/1008-682x.170445
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发表时间：
2016-03
影响因子：
2.9
通讯作者：
Sabanegh E
中科院分区：
文献类型：
--
作者：
Agarwal A;Sharma R;Samanta L;Durairajanayagam D;Sabanegh E
应用比较蛋白质组学方法研究精索静脉曲张不育男性精子蛋白分布的主要差异及其表达水平的验证。结合每个精索静脉曲张结果的研究特异性估计，以确定与临床精索静脉曲张分期和侧边性无关的男性精索静脉曲张相关不育相关的蛋白质。Western blotting检测包括分子伴侣在内的与应激反应和精子功能相关的5个关键蛋白（PKAR1A、AK7、CCT6B、HSPA2、ODF2）的表达水平。精索静脉曲张组有99种蛋白差异表达。超过87%参与主要能量代谢和精子关键功能的DEP在精索静脉曲张组中表达不足。精索静脉曲张组受影响的关键蛋白质功能是精子发生、精子活力和线粒体功能障碍，Western blotting进一步验证了这一点，证实了蛋白质组学分析。精索静脉曲张本质上是由于血供受损导致的能量剥夺、缺氧和高热状态，脂质代谢、线粒体电子传递链和克雷布斯循环酶下调证实了这一点。为了证实蛋白质组学分析，用Western blotting验证了5个鉴定的感兴趣蛋白的表达。本研究有助于建立基于分子参数的生物标志物“指纹”来评估精子质量。
To study the major differences in the distribution of spermatozoa proteins in infertile men with varicocele by comparative proteomics and validation of their level of expression. The study-specific estimates for each varicocele outcome were combined to identify the proteins involved in varicocele-associated infertility in men irrespective of stage and laterality of their clinical varicocele. Expression levels of 5 key proteins (PKAR1A, AK7, CCT6B, HSPA2, and ODF2) involved in stress response and sperm function including molecular chaperones were validated by Western blotting. Ninety-nine proteins were differentially expressed in the varicocele group. Over 87% of the DEP involved in major energy metabolism and key sperm functions were underexpressed in the varicocele group. Key protein functions affected in the varicocele group were spermatogenesis, sperm motility, and mitochondrial dysfunction, which were further validated by Western blotting, corroborating the proteomics analysis. Varicocele is essentially a state of energy deprivation, hypoxia, and hyperthermia due to impaired blood supply, which is corroborated by down-regulation of lipid metabolism, mitochondrial electron transport chain, and Krebs cycle enzymes. To corroborate the proteomic analysis, expression of the 5 identified proteins of interest was validated by Western blotting. This study contributes toward establishing a biomarker “fingerprint” to assess sperm quality on the basis of molecular parameters.
人精液中附睾蛋白酶抑制剂与纤连蛋白的相关性
影响因子：
3.7
作者：
Zhang X;Fang J;Xu B;Zhang S;Su S;Song Z;Deng Y;Wang H;Zhao D;Niu X;Wang Z
通讯作者：
Wang Z