Department of Medicine and Medical Specialities, (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain.
Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.
Biomolecules. 2024 Sep 30;14(10):1237. doi: 10.3390/biom14101237.
Preeclampsia (PE) is a complex multisystem disease characterized by hypertension of sudden onset (>20 weeks' gestation) coupled with the presence of at least one additional complication, such as proteinuria, maternal organ dysfunction, or uteroplacental dysfunction. Hypertensive states during pregnancy carry life-threatening risks for both mother and baby. The pathogenesis of PE develops due to a dysfunctional placenta with aberrant architecture that releases factors contributing to endothelial dysfunction, an antiangiogenic state, increased oxidative stress, and maternal inflammatory responses. Previous studies have shown a correlation between grade 3 placental calcifications and an elevated risk of developing PE at term. However, little is known about the molecular pathways leading to placental calcification. In this work, we studied the gene and protein expression of c-Jun N-terminal kinase (JNK), Runt-related transcription factor 2 (RUNX2), osteocalcin (OSC), osteopontin (OSP), pigment epithelium-derived factor (PEDF), MSX-2/HOX8, SOX-9, WNT-1, and β-catenin in placental tissue from women with late-onset PE (LO-PE). In addition, we employed von Kossa staining to detect mineral deposits in placental tissues. Our results show a significant increase of all these components in placentas from women with LO-PE. Therefore, our study suggests that LO-PE may be associated with the activation of molecular pathways of placental calcification. These results could be the starting point for future research to describe the molecular mechanisms that promote placental calcification in PE and the development of therapeutic strategies directed against it.
子痫前期 (PE) 是一种复杂的多系统疾病，其特征为突然发作的高血压（>20 周妊娠），并伴有至少一种其他并发症，如蛋白尿、母体器官功能障碍或胎盘功能障碍。妊娠期间的高血压状态对母婴均有生命威胁。PE 的发病机制是由于胎盘功能失调，结构异常，释放出导致内皮功能障碍、抗血管生成状态、氧化应激增加和母体炎症反应的因子。先前的研究表明，胎盘 3 级钙化与足月时发生 PE 的风险升高之间存在相关性。然而，对于导致胎盘钙化的分子途径知之甚少。在这项工作中，我们研究了 c-Jun N-末端激酶 (JNK)、 runt 相关转录因子 2 (RUNX2)、骨钙素 (OSC)、骨桥蛋白 (OSP)、色素上皮衍生因子 (PEDF)、MSX-2/HOX8、SOX-9、WNT-1 和 β-连环蛋白在晚发型子痫前期 (LO-PE) 妇女的胎盘组织中的基因和蛋白表达。此外，我们还采用 von Kossa 染色来检测胎盘组织中的矿物质沉积。我们的结果表明，LO-PE 妇女的胎盘组织中所有这些成分的表达均显著增加。因此，我们的研究表明，LO-PE 可能与胎盘钙化的分子途径激活有关。这些结果可能是未来研究描述促进 PE 中胎盘钙化的分子机制以及针对其开发治疗策略的起点。
