Department of Obstetrics, Shenzhen Maternity and Child Healthcare Hospital, Cheeloo College of Medicine, Shandong University, Shenzhen, Guangdong, P.R. China.
Department of Obstetrics and Gynaecology, Shandong Provincial Maternal and Child Health Care Hospital, Cheeloo College of Medicine, Shandong University, Jinan, P.R. China.
J Perinat Med. 2023 Sep 12;52(1):41-49. doi: 10.1515/jpm-2022-0565. Print 2024 Jan 29.
Preeclampsia (PE) is a disease specific to pregnancy that causes 9-10 % of maternal deaths. Early-onset PE (<34 weeks' gestation) is the most dangerous category of PE. Wnt7a and GPR124 (G protein-coupled receptor 124) are widely expressed in the human reproductive process. Especially during embryogenesis and tumorigenesis, Wnt7a plays a crucial role. However, few studies have examined the association between Wnt7a-GPR124 and early-onset PE. The aim of this study was to examine the significance of Wnt7a and GPR124 in early-onset PE as well as Wnt7a's role in trophoblast cells.
Immunohistochemistry (IHC), real-time PCR, and western blotting (WB) were used to investigate Wnt7a and GPR124 expression in normal and early-onset PE placentas. Additionally, FACS, Transwell, and CCK-8 assays were used to diagnose Wnt7a involvement in migration, invasion, and proliferation.
In the early-onset PE group, Wnt7a and GPR124 expression was significantly lower than in the normal group, especially in the area of syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs). A negative correlation was found between Wnt7a RNA and GPR124 expression (r=-0.42, p<0.01). However, the Wnt7a RNA expression level was positive correlated with PE severity. In further cellular functional experiments, knockdown of Wnt7a inhibits HTR8/SVeno cells invasion and migration but has little effect on proliferation and apoptosis.
Through the Wnt pathway, Wnt7a regulates trophoblast cell invasion and migration, and may contribute to early-onset preeclampsia pathogenesis. A molecular level study of Wnt7a will be needed to find downstream proteins and mechanisms of interaction.
子痫前期（PE）是一种特有的妊娠疾病，导致 9-10%的孕产妇死亡。早发型 PE（<34 周妊娠）是最危险的 PE 类别。Wnt7a 和 GPR124（G 蛋白偶联受体 124）广泛表达于人类生殖过程中。特别是在胚胎发生和肿瘤发生过程中，Wnt7a 发挥着关键作用。然而，关于 Wnt7a-GPR124 与早发型 PE 的相关性研究较少。本研究旨在探讨 Wnt7a 和 GPR124 在早发型 PE 中的意义以及 Wnt7a 在滋养细胞中的作用。
采用免疫组织化学（IHC）、实时 PCR 和 Western blot（WB）检测正常和早发型 PE 胎盘组织中 Wnt7a 和 GPR124 的表达。此外，还采用 FACS、Transwell 和 CCK-8 检测 Wnt7a 对迁移、侵袭和增殖的影响。
在早发型 PE 组中，Wnt7a 和 GPR124 的表达明显低于正常组，尤其是在合体滋养层（STB）和绒毛外滋养层（EVT）中。Wnt7a RNA 与 GPR124 表达呈负相关（r=-0.42，p<0.01）。然而，Wnt7a RNA 表达水平与 PE 严重程度呈正相关。在进一步的细胞功能实验中，敲低 Wnt7a 抑制 HTR8/SVeno 细胞侵袭和迁移，但对增殖和凋亡影响不大。
通过 Wnt 通路，Wnt7a 调节滋养细胞的侵袭和迁移，可能参与早发型子痫前期的发病机制。需要对 Wnt7a 进行分子水平的研究，以找到下游蛋白和相互作用机制。
