Department of Surgery, Division of Urology, Human Reproduction Section, Universidade Federal de São Paulo, São Paulo, Brazil.
Fleury Group, Av. Gal Valdomiro de Lima, 508, São Paulo 04344-070, Brazil.
J Proteomics. 2019 Mar 30;196:22-32. doi: 10.1016/j.jprot.2019.01.019. Epub 2019 Jan 30.
Varicocelectomy is associated to improved semen quality and sperm functional quality, but individual response is highly variable. Thus, a prospective study was performed including 25 men who collected a semen sample before and 12 months after subinguinal microsurgical varicocelectomy. Semen analysis, sperm functional analysis, and seminal plasma proteomic analysis was performed before and 12 months after varicocelectomy, and according to improvement or not of semen quality (positive and negative outcome). Varicocelectomy led to an increase in semen volume and sperm count, morphology, and mitochondrial activity. In the pre- vs. post-samples, 698 proteins were quantified - 91 differentially expressed after varicocelectomy. In the positive vs. negative outcome analysis, 647 proteins were identified - 151 differentially expressed in the negative outcome group and 30 differentially expressed in the positive outcome group. Tripeptidyl peptidase-1 offered a predictive value for outcome, with an area under a ROC curve of 84.5%. It seems TPP1 is an outcome predictor for varicocelectomy in adults. More importantly, this study demonstrates that the seminal plasma proteome is different in men with varicocele when compared to post-treatment samples from the same individuals. Understanding and monitoring the molecular mechanisms of semen may further establish therapeutic options for these men. SIGNIFICANCE: Although several large-scale studies have demonstrated varicocele is unequivocally associated to male infertility, these same studies have also demonstrated that varicocele is not a determinant of male infertility. We have yet to answer the question of why don't all men with varicocele present with infertility. Varicocele treatment improves semen quality, but its results are variable, and one cannot know who will and who will not benefit from surgical treatment. Results from this study strongly advance a concept that our previous studies have shown: that men with varicocele present an inflammatory semen profile. We have further demonstrated that men operated for varicocele present a decrease in this inflammatory profile, and that when they do not, semen quality remains unaltered. Trypeptidil peptidase-1, a seminal protein, was 3-fold higher in men with a positive outcome after the procedure, when compared to men with a negative outcome. Therefore, inflammation seems to be a central point to varicocele-derived male infertility.
精索静脉结扎术可改善精液质量和精子功能，但个体反应差异很大。因此，进行了一项前瞻性研究，纳入了 25 名男性，他们在精索静脉结扎术前和术后 12 个月收集了精液样本。在精索静脉结扎术前和术后 12 个月进行了精液分析、精子功能分析和精浆蛋白质组学分析，并根据精液质量的改善（阳性和阴性结果）进行了分析。精索静脉结扎术后精液量、精子计数、形态和线粒体活性均增加。在术前与术后样本中，共定量了 698 种蛋白质 - 精索静脉结扎术后有 91 种蛋白质表达差异。在阳性与阴性结果分析中，共鉴定了 647 种蛋白质 - 在阴性结果组中有 151 种蛋白质表达差异，在阳性结果组中有 30 种蛋白质表达差异。三肽基肽酶-1 对结果有预测价值，ROC 曲线下面积为 84.5%。似乎 TPP1 是成人精索静脉结扎术的结果预测因子。更重要的是，这项研究表明，与同一男性治疗后的样本相比，精索静脉曲张男性的精浆蛋白质组不同。了解和监测精液的分子机制可能会为这些男性进一步建立治疗选择。意义：尽管几项大规模研究表明精索静脉曲张与男性不育明确相关，但这些研究也表明精索静脉曲张不是男性不育的决定因素。我们仍未回答为什么并非所有精索静脉曲张男性都存在不育问题。精索静脉结扎术可改善精液质量，但效果不一，且无法知道谁将受益于手术治疗。本研究结果有力地提出了我们之前的研究已经表明的一个概念：精索静脉曲张男性的精液呈炎症性特征。我们进一步证明，接受精索静脉结扎术的男性的这种炎症特征减少，而当他们没有这种特征时，精液质量仍保持不变。三肽基肽酶-1 是一种精液蛋白，术后结果阳性的男性比结果阴性的男性高 3 倍。因此，炎症似乎是精索静脉曲张导致男性不育的一个核心问题。
