New insights about the early diagnosis of fertility impairment in varicoceles: The DNA repair gene example
New insights about the early diagnosis of fertility impairment in varicoceles: The DNA repair gene example
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关于精索静脉曲张生育障碍早期诊断的新见解：DNA 修复基因示例
DOI：
10.1016/j.mehy.2012.01.029
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发表时间：
2012-04-01
影响因子：
4.7
通讯作者：
Li, Wei
中科院分区：
文献类型：
--
作者：
Guo, Sheng-jie;Sun, Zhi-jian;Li, Wei
在所有因不育而就诊的男性中，约30%的人似乎患有精索静脉曲张，因此，这种男性功能障碍被认为是许多患者不育的潜在原因。新的研究指出，精子的前进运动是最重要的预测生育能力的指标，如果分析是在不育持续时间内进行的，那么评估精索静脉曲张非常早期的自发性睾丸损害就没有解决的问题。由于精索静脉曲张引起的睾丸功能恶化是进行性的，早期有效地评估精索静脉曲张对这一人群未来的医疗干预具有重要意义。精索静脉曲张影响睾丸功能的机制尚不清楚，但睾丸温度升高是最普遍接受的病因。在这种背景下，我们假设转移相关蛋白1(MTA1)是一种内在的DNA损伤反应成分，在初级精母细胞中对热应激具有瞬时保护作用，有可能成为评估精索静脉曲张早期睾丸损伤的诊断生物标志物。热应激后MTA1表达的降低远远早于细胞凋亡波的开始，这为其在生物化学应用中的理论合理性和技术可行性提供了依据。基本上，MTA1通过上调P53的脱乙酰化水平来参与维持热刺激诱导的早期凋亡平衡，P53是负责高温诱导生殖细胞凋亡的初始阶段的主要调节因子。这些知识共同促进了我们的信念，即来自未来实验的信息，旨在进一步研究精子发生过程中的MTA1，将为开发一种新的生物标记物来早期诊断精索静脉曲张的睾丸损害提供科学基础，这将有助于改善这种进行性病理的结果。(C)2012爱思唯尔有限公司。保留所有权利。
Of all men consulted for infertility, around 30% appear to have a varicocele, therefore, this male dysfunction has been considered as a potential cause of infertility in many patients. Emerging studies point out spermatozoa progressive motility as the most important predictor of fertility provided that the analysis was carried out with infertility duration, thus leaving unsolved problem to evaluate the spontaneous testicular damage during the very early phase in varicoceles. Given the deterioration of testicular function caused by varicoceles is progressive, the early and efficient evaluation of testicular damage would be of great importance for the future medical intervention in this population. The resultant mechanism by which varicoceles affect testicular function remains unclear, but the increase in testicular temperature is most commonly accepted aetiology. In this context, we hypothesize that metastasis-associated protein 1 (MTA1), an intrinsic DNA damage response component, possessing transient protective effect in primary spermatocytes against heat stress, bears the potential to be a diagnostic biomarker for the assessment of early testicular damage in varicoceles. The facet that the decrease of MTA1 expression appears much earlier than the beginning of apoptotic wave after heat stress warrants its theoretical rationality and technical accessibility for biochemical application. Basically, MTA1 participates in the maintenance of early apoptotic balance induced by hyperthermal stimulation by elevating the deacetylation level of p53, a master regulator responsible for the initial phase of germ cell apoptosis induced by hyperthermia. These knowledges collectively promote our belief that information from future experiments designed to further study MTA1 during spermatogenesis will provide a scientific basis for the development of a novel biomarker for early diagnosis of testicular detriment in varicoceles, which should lead to improved outcomes in this progressive pathology. (C) 2012 Elsevier Ltd. All rights reserved.