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在具有炎症基础的生殖病理中,F-异前列腺素是否比丙二醛更适合作为精液脂质过氧化的标志物?

Are F-isoprostanes a better marker of semen lipid peroxidation than MDA in reproductive pathologies with inflammatory basis?

作者信息

Moretti Elena, Signorini Cinzia, Menchiari Silvia, Liguori Laura, Corsaro Roberta, Gambera Laura, Collodel Giulia

机构信息

Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy.

Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy.

出版信息

Cytokine. 2025 Apr;188:156889. doi: 10.1016/j.cyto.2025.156889. Epub 2025 Feb 8.

Abstract

Many male reproductive pathologies and a part of undiagnosed infertility share an oxidative stress (OS) etiology with high reactive oxygen species and cytokine concentrations. The lack of reliable biomarkers to quantify oxidative injury is a crucial problem in the field of male infertility. In this observational study, IL-1β and the OS markers malondialdehyde (MDA) and F-isoprostanes (F-IsoPs) were quantified in seminal plasma of 46 infertile patients with varicocele, genitourinary infections, idiopathic infertility, and 11 fertile men. Semen analysis was performed following WHO guidelines, IL-1β was determined by ELISA, MDA was quantified by HPLC, and F-IsoPs by GC/NICI-MS analysis. F-IsoPs were immunolocalized in spermatozoa of fertile and infertile subjects. Results indicated that F-IsoP, MDA, and IL-1β seminal levels positively correlated pairwise (p < 0.001) and showed negative correlations with sperm parameters (p < 0.001). Then, the studied population was grouped following the cause of infertility and the variables were compared between the different groups and a control sample. Seminal IL-1β, F-IsoPs, and MDA were significantly higher in varicocele (p < 0.001, for MDA p < 0.01) and genitourinary infections (p < 0.001, for IL-1β p < 0.01) groups than those observed in fertile subjects. F-IsoPs seemed to discriminate more accurately than MDA the different conditions, in particular idiopathic infertility. ROC curves demonstrated that the three analyzed indices were able to discriminate fertile and infertile patients. The immunofluorescence studies showed a low presence of F-IsoPs in spermatozoa of fertile men and an evident labeling in the tail, and cytoplasmic residues of spermatozoa from infertile patients. In conclusion, this data confirmed that F-IsoP level is a suitable marker of OS in seminal plasma, even more accurate than MDA and can be proposed for measuring OS in the clinical setting.

摘要

许多男性生殖系统疾病以及部分不明原因的不育症都与氧化应激(OS)病因有关,其特征是活性氧和细胞因子浓度较高。缺乏可靠的生物标志物来量化氧化损伤是男性不育领域的一个关键问题。在这项观察性研究中,对46名患有精索静脉曲张、泌尿生殖系统感染、特发性不育症的不育患者以及11名有生育能力的男性的精液中白细胞介素-1β(IL-1β)以及氧化应激标志物丙二醛(MDA)和F-异前列腺素(F-IsoPs)进行了定量分析。精液分析按照世界卫生组织的指南进行,IL-1β通过酶联免疫吸附测定法(ELISA)测定,MDA通过高效液相色谱法(HPLC)定量,F-IsoPs通过气相色谱/负离子化学电离质谱(GC/NICI-MS)分析。F-IsoPs在有生育能力和不育受试者的精子中进行了免疫定位。结果表明,精液中F-IsoP、MDA和IL-1β水平两两呈正相关(p < 0.001),并且与精子参数呈负相关(p < 0.001)。然后,根据不育原因对研究人群进行分组,并在不同组与对照样本之间比较变量。精索静脉曲张组(MDA的p < 0.01)和泌尿生殖系统感染组(IL-1β的p < 0.01)的精液IL-1β、F-IsoPs和MDA显著高于有生育能力的受试者。F-IsoPs似乎比MDA更能准确区分不同情况,尤其是特发性不育症。受试者工作特征(ROC)曲线表明,这三个分析指标能够区分有生育能力和不育的患者。免疫荧光研究显示,有生育能力男性的精子中F-IsoPs含量较低,而不育患者精子的尾部和细胞质残留中有明显的标记。总之,这些数据证实F-IsoP水平是精液中氧化应激的合适标志物,甚至比MDA更准确,可用于临床环境中氧化应激的测量。

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