Kaltsas Aris, Zikopoulos Athanasios, Markou Eleftheria, Zachariou Athanasios, Stavropoulos Marios, Kratiras Zisis, Symeonidis Evangelos N, Dimitriadis Fotios, Sofikitis Nikolaos, Chrisofos Michael
Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece.
Department of Obstetrics and Gynecology, Royal Cornwall Hospital, Truro TR1 3LJ, UK.
J Clin Med. 2024 Dec 4;13(23):7390. doi: 10.3390/jcm13237390.
Varicoceles are a common contributor to male infertility, significantly impacting male-factor infertility cases. Traditional diagnostic methods often lack the sensitivity to detect the molecular and cellular disruptions caused by varicoceles, limiting the development of effective, personalized treatments. This narrative review aims to explore the advancements in proteomics and metabolomics as innovative, non-invasive diagnostic tools for varicocele-associated male infertility and their potential in guiding personalized therapeutic strategies. A comprehensive literature search was conducted using databases such as PubMed, Scopus, and Web of Science up to October 2024. Studies focusing on the application of proteomic and metabolomic analyses in varicocele-associated male infertility were selected. The findings were critically analyzed to synthesize current knowledge and identify future research directions. Proteomic analyses revealed differentially expressed proteins in the sperm and seminal plasma of varicocele patients, revealing disruptions in pathways related to oxidative stress, mitochondrial dysfunction, apoptosis, and energy metabolism. Key proteins such as heat shock proteins, mitochondrial enzymes, and apoptotic regulators were notably altered. Metabolomic profiling uncovered specific metabolites in seminal plasma-such as decreased levels of lysine, valine, and fructose-that correlate with impaired sperm function and fertility potential. The integration of proteomic and metabolomic data provides a comprehensive molecular fingerprint of varicocele-induced infertility, facilitating the identification of novel biomarkers for early diagnosis and the development of personalized therapeutic interventions. Advances in proteomics and metabolomics have significantly enhanced our understanding of the molecular mechanisms underlying varicocele-associated male infertility. These "omics" technologies hold great promise for improving diagnostic accuracy and personalizing treatment, ultimately leading to better outcomes for affected men. Future large-scale clinical trials and validations are essential to confirm these biomarkers and facilitate their integration into routine clinical practice.
精索静脉曲张是男性不育的常见原因，对男性因素导致的不育病例有重大影响。传统诊断方法往往缺乏检测精索静脉曲张引起的分子和细胞破坏的敏感性，限制了有效、个性化治疗方法的开发。本叙述性综述旨在探讨蛋白质组学和代谢组学作为精索静脉曲张相关性男性不育的创新、非侵入性诊断工具的进展，以及它们在指导个性化治疗策略方面的潜力。截至2024年10月，使用PubMed、Scopus和Web of Science等数据库进行了全面的文献检索。选择了关注蛋白质组学和代谢组学分析在精索静脉曲张相关性男性不育中的应用的研究。对研究结果进行了批判性分析，以综合当前知识并确定未来的研究方向。蛋白质组学分析揭示了精索静脉曲张患者精子和精浆中差异表达的蛋白质，揭示了与氧化应激、线粒体功能障碍、细胞凋亡和能量代谢相关的通路的破坏。热休克蛋白、线粒体酶和凋亡调节因子等关键蛋白质有明显改变。代谢组学分析发现精浆中的特定代谢物，如赖氨酸、缬氨酸和果糖水平降低，这些代谢物与精子功能受损和生育潜力相关。蛋白质组学和代谢组学数据的整合提供了精索静脉曲张所致不育的全面分子指纹，有助于识别早期诊断的新型生物标志物并开发个性化治疗干预措施。蛋白质组学和代谢组学的进展显著增强了我们对精索静脉曲张相关性男性不育潜在分子机制的理解。这些“组学”技术在提高诊断准确性和实现治疗个性化方面具有巨大潜力，最终为受影响的男性带来更好的治疗效果。未来的大规模临床试验和验证对于确认这些生物标志物并促进其融入常规临床实践至关重要。
