Wei Yingying, Tian Haojun, Wei Xuancheng, Zhang Ai, Wei Mengtian, Wang Ruixue, Zhang Lu, Qiao Ping, Wang Kai
Clinical and Translational Research Center, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Fetal Medicine Center, Qingdao Women and Children's Hospital, Qingdao University, Qingdao, 266000, China.
Eur J Med Res. 2024 Dec 31;29(1):642. doi: 10.1186/s40001-024-02223-6.
Preeclampsia (PE) is a pregnancy-specific, multisystemic disorder that affects 2-8% pregnancies worldwide and is a leading cause of maternal and perinatal mortality. At present, there is no cure for PE apart from delivery the placenta. Therefore, it is important and urgent to possess a suitable animal model to study the pathology and treatment of PE. When exogenous soluble fms-like tyrosine kinase-1 (sFlt-1) is administered, pregnant animals develop a PE-like phenotype. However, there is no report on the comparison between different methods of constructing PE mouse models using sFlt-1.
In this study, the adenovirus carrying sFlt-1(ADV-Flt-1) and recombinant murine sFlt-1 protein (RM Flt-1) are two different methods were used to induce and compare PE-like mouse models. Pregnancy outcomes were examined on E14.5 and E17.5.
Our data showed that on E14.5, the adenovirus carrying sFlt-1 induced PE-like phenotype, whereas recombinant murine sFlt-1 protein not. On E17.5, both the two methods induced PE-like phenotype including hypertension, proteinuria, fetal growth restriction, placental and glomerular endotheliosis. Importantly, in the adenoviral-mediated sFlt-1 group, the circulating concentration of sFlt-1 were higher than in the recombinant sFlt-1 group, leading to earlier and more severe symptoms of PE. The ADV-Flt-1 group is easy to operate, quickly effective and efficient. The RM Flt-1 group is safer and more stable, with good repeatability, but slower to take effect.
We proposed that the adenoviral-mediated sFlt-1 model can better simulate early-onset and severe PE.
子痫前期（PE）是一种与妊娠相关的多系统疾病，全球2%-8%的妊娠会受其影响，是孕产妇和围产儿死亡的主要原因。目前，除了娩出胎盘外，尚无治愈PE的方法。因此，拥有合适的动物模型来研究PE的病理和治疗方法至关重要且迫在眉睫。当给予外源性可溶性fms样酪氨酸激酶-1（sFlt-1）时，妊娠动物会出现类似PE的表型。然而，尚无关于使用sFlt-1构建PE小鼠模型的不同方法之间比较的报道。
在本研究中，携带sFlt-1的腺病毒（ADV-Flt-1）和重组鼠sFlt-1蛋白（RM Flt-1）是用于诱导和比较类似PE小鼠模型的两种不同方法。在胚胎第14.5天（E14.5）和第17.5天（E17.5）检查妊娠结局。
我们的数据显示，在E-14.5时，携带sFlt-1的腺病毒诱导出类似PE的表型，而重组鼠sFlt-1蛋白则未诱导出。在E17.5时，两种方法均诱导出类似PE的表型，包括高血压、蛋白尿、胎儿生长受限、胎盘和肾小球内皮病变。重要的是，在腺病毒介导的sFlt-1组中，sFlt-1的循环浓度高于重组sFlt-1组，导致PE症状出现更早、更严重。ADV-Flt-1组操作简便、起效快且效率高。RM Flt-1组更安全、更稳定，重复性好，但起效较慢。
我们认为腺病毒介导的sFlt-1模型能更好地模拟早发型和重度PE。
