Department of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, Mickiewicza 2D, 15-222 Bialystok, Poland.
Department of Immunology, Medical University of Bialystok, Waszyngtona 15A, 15-269 Bialystok, Poland.
Int J Mol Sci. 2024 Sep 29;25(19):10513. doi: 10.3390/ijms251910513.
Despite significant advances in prenatal medicine, spontaneous miscarriage remains one of the most common and serious pregnancy complications, affecting an increasing number of women. Since many aspects of the pathogenesis of spontaneous miscarriage remain unexplained, the aim of this study has been to assess the involvement of the NLRP3 inflammasome as a potential causative factor. The concentrations of NLRP3, IL-1β, IL-18, and cytochrome C in the serum of patients after miscarriage were measured by means of the immunoenzymatic method. In the placental tissue, the expression of NLRP3, IL-1β, IL-18, and Caspase-1 as well as that of the classical apoptosis biomarkers Fas, FasL, Bcl-2, and Ca was evaluated by means of immunohistochemistry techniques. Additionally, in whole blood, the concentrations of elements crucial for pregnancy progression, such as Ca, K, Mg, and Na, were examined by means of the ICP-OES method. Significantly higher concentrations of NLRP3 and IL-18 were demonstrated in the serum of patients with miscarriage as compared to the control group. In the placental tissue samples, a higher expression of IL-1β, IL-18, and Caspase-1 proteins was noted in women who had experienced miscarriage as compared to the control group. At the same time, a significantly lower expression of FasL and Bcl-2 proteins as well as Ca deposits was observed in women after miscarriage as compared to those with a normal pregnancy outcome. Significantly lower concentrations of Ca and K were recorded in the blood of patients with spontaneous miscarriage as compared to pregnant women. The analysis of the results x indicated a greater involvement of the inflammasome in women with spontaneous miscarriage associated with oxidative-antioxidative imbalance than in the case of miscarriage related to NET formation. Our research has provided evidence for the involvement of the inflammasome in the process of spontaneous miscarriage and identifies a new direction for diagnostics that includes NLRP3 as a preventive element in prenatal care, particularly in light of the steadily declining number of pregnancies and the increasing number of reproductive failures.
尽管产前医学取得了重大进展，但自然流产仍然是最常见和最严重的妊娠并发症之一，越来越多的女性受到影响。由于自然流产发病机制的许多方面仍未得到解释，本研究旨在评估 NLRP3 炎性体作为潜在致病因素的作用。通过免疫酶法测定流产后患者血清中 NLRP3、IL-1β、IL-18 和细胞色素 C 的浓度。通过免疫组织化学技术评估 NLRP3、IL-1β、IL-18 和 Caspase-1 以及经典凋亡生物标志物 Fas、FasL、Bcl-2 和 Ca 在胎盘组织中的表达。此外，通过电感耦合等离子体发射光谱法（ICP-OES）检测全血中对妊娠进展至关重要的元素（如 Ca、K、Mg 和 Na）的浓度。与对照组相比，流产患者血清中 NLRP3 和 IL-18 的浓度明显升高。与对照组相比，流产组胎盘组织中 IL-1β、IL-18 和 Caspase-1 蛋白的表达更高。同时，流产组 FasL 和 Bcl-2 蛋白以及 Ca 沉积的表达明显低于正常妊娠结局组。与正常妊娠的孕妇相比，自然流产患者的血液中 Ca 和 K 的浓度明显降低。结果分析表明，与 NET 形成相关的流产相比，自然流产患者中炎性体的参与程度更大，与氧化-抗氧化失衡有关。我们的研究为炎性体在自然流产过程中的参与提供了证据，并确定了一种新的诊断方向，将 NLRP3 作为产前保健的预防因素，特别是考虑到妊娠数量不断下降和生殖失败数量不断增加的情况。
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