Department of Biology, Genetics Unit, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
Biomedical Research Institute of Lleida (IRBLLEIDA), +Pec Proteomics Research Group (+PPRG), Neuroscience Area, University Hospital Arnau de Vilanova (HUAV), Lleida, Spain.
Front Endocrinol (Lausanne). 2023 Mar 22;14:1113824. doi: 10.3389/fendo.2023.1113824. eCollection 2023.
Extracellular vesicles (EVs) have been recognized as key players in numerous physiological functions. These vesicles alter their compositions attuned to the health and disease states of the organism. In men, significant changes in the proteomic composition(s) of seminal plasma EVs (sEVs) have already been found to be related to infertility.
Methods: In this study, we analyze the posttranslational configuration of sEV proteomes from normozoospermic (NZ) men and non-normozoospermic (non-NZ) men diagnosed with teratozoospermia and/or asthenozoospermia by unbiased, discovery-driven proteomics and advanced bioinformatics, specifically focusing on citrulline (Cit) and homocitrulline (hCit) posttranscriptional residues, both considered product of ureido protein modifications.
Significant increase in the proteome-wide cumulative presence of hCit together with downregulation of Cit in specific proteins related to decisive molecular functions have been encountered in sEVs of non-NZ subjects. These findings identify novel culprits with a higher chance of affecting fundamental aspects of sperm functional quality and define potential specific diagnostic and prognostic non-invasive markers for male infertility.
细胞外囊泡 (EVs) 已被认为是许多生理功能的关键参与者。这些囊泡会根据生物体的健康和疾病状态来调整其组成。在男性中，已经发现精液 EVs（sEVs）的蛋白质组组成发生显著变化与不育有关。
在这项研究中，我们通过无偏见的、发现驱动的蛋白质组学和先进的生物信息学分析了来自正常精子（NZ）男性和被诊断为畸形精子症和/或弱精子症的非正常精子（非 NZ）男性的 sEV 蛋白质组的翻译后结构，特别是关注瓜氨酸（Cit）和同型瓜氨酸（hCit）转录后残基，两者都被认为是脲基蛋白修饰的产物。
在非 NZ 受试者的 sEV 中，我们遇到了 hCit 在蛋白质组范围内的累积存在显著增加，而与决定性分子功能相关的特定蛋白质中的 Cit 下调。这些发现确定了具有更高可能性影响精子功能质量基本方面的新罪魁祸首，并定义了潜在的男性不育症特定的非侵入性诊断和预后标志物。
