Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Skopje, North Macedonia.
Laboratory for Histopathology, Clinical Hospital "Sistina", Skopje, North Macedonia.
Proteomics Clin Appl. 2024 Nov;18(6):e202400020. doi: 10.1002/prca.202400020. Epub 2024 Aug 25.
Recurrent pregnancy loss (RPL) represents a common disorder with consequences on family and society. As more than half of the RPL cases do not have a clearly identified cause, uncovering the mechanisms behind the idiopathic RPL is urgently needed.
Using label-free data-independent LC-MS/MS acquisition coupled with ion mobility, we compared the proteome of chorionic villi from 13 RPL cases with 10 age and gestational week-matched elective pregnancies. Transcriptional levels of selected candidate biomarkers were determined in chorionic villi of 35 RPL cases and 25 controls using quantitative polymerase chain reaction (qPCR).
Statistically significant difference in abundance (Benjamini-Hochberg [B-H] p ≤ 0.05) and fold change ≥1.5 showed 128 proteins. Bioinformatics analysis identified complement and coagulation cascades, platelet activation, tricarboxylic acid cycle (TCA) cycle, and ferroptosis as pathways with the highest significance. Correlation with transcriptome datasets revealed a weak statistically significant positive correlation with 45% of the co-differentially expressed proteins/genes displaying the same regulation trend. The transcription levels of neurofilament light polypeptide (NEFL), dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex_mitochondrial (DLST), nitric oxide synthase 3 (NOS3), and ceruloplasmin (CP) were significantly increased in the RPL, consistent with the proteomics findings.
Our data suggests alteration of several pathways as potential causes of idiopathic RPL from the fetal side and opens the way for investigations concerning clinical management.
复发性妊娠丢失（RPL）是一种常见的疾病，对家庭和社会都有影响。由于超过一半的 RPL 病例没有明确的病因，因此迫切需要揭示特发性 RPL 的背后机制。
使用无标签的、数据独立的 LC-MS/MS 采集方法结合离子淌度，我们比较了 13 例 RPL 病例和 10 例年龄和妊娠周匹配的选择性妊娠的绒毛组织的蛋白质组。使用定量聚合酶链反应（qPCR）在 35 例 RPL 病例和 25 例对照的绒毛组织中测定了选定候选生物标志物的转录水平。
统计学上显著差异的丰度（Benjamini-Hochberg [B-H] p ≤ 0.05）和倍数变化≥1.5 显示了 128 种蛋白质。生物信息学分析确定补体和凝血级联、血小板激活、三羧酸循环（TCA）循环和铁死亡作为具有最高意义的途径。与转录组数据集的相关性表明，45%的共同差异表达蛋白/基因显示出相同的调节趋势，与相关性较弱但统计学上显著正相关。神经丝轻多肽（NEFL）、二氢脂酰基辅酶 A 脱氢酶复合体成分赖氨酸残基琥珀酰转移酶线粒体（DLST）、一氧化氮合酶 3（NOS3）和铜蓝蛋白（CP）的转录水平在 RPL 中显著增加，与蛋白质组学结果一致。
我们的数据表明，从胎儿方面来看，几种途径的改变可能是特发性 RPL 的原因，并为有关临床管理的研究开辟了道路。
