Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Department of Reproductive Medicine, Hainan Provincial Clinical Research Center for Thalassemia, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan, China.
J Gene Med. 2020 Dec;22(12):e3273. doi: 10.1002/jgm.3273. Epub 2020 Oct 1.
Pre-eclampsia (PE) is a major cause of maternal and neonatal mortality and morbidity. Abnormal invasion of trophoblast cells is a major pathogenesis observed in PE. In the present study, we aimed to explore the association between forkhead box A1 (FOXA1) and early-onset pre-eclampsia (EOPE) and to determine the effects of FOXA1 on trophoblast cell apoptosis, migration and invasion.
Clinical data and placentas of patients with EOPE and normal pregnant women were collected in the First Affiliated Hospital of Hainan Medical College. The protein expression levels of FOXA1 in the clinical samples were evaluated by western blotting and immunohistochemistry. The effects of FOXA1 knockdown on HTR-8/SVneo cell apoptosis, migration and invasion were evaluated by flow cytometry, wound healing and transwell invasion assays, respectively.
The western blot and immunohistochemical analysis showed that FOXA1 protein expression in placenta of EOPE group was significantly lower than that of normal group. The expression of FOXA1 in the placentas of EOPE and normal pregnant women was negatively correlated with systolic pressure and diastolic pressure. The expression of FOXA1 in EOPE and normal pregnant women was positively correlated with gestation weeks at delivery and neonatal birthweight. In vitro functional studies showed that silencing FOXA1 increased apoptosis, and inhibited the migration and invasion of HTR-8/SVneo cells.
Down-regulation of FOXA1 in the placentas may indicate poor prognosis of EOPE. Silencing of FOXA1 induced apoptosis in trophoblast cells, and impaired the migratory and invasive capacity of trophoblast cells. FOXA1 may represent a potential therapeutic target for EOPE.
子痫前期（PE）是孕产妇和新生儿死亡和发病的主要原因。滋养细胞异常浸润是 PE 的主要发病机制。本研究旨在探讨叉头框转录因子 A1（FOXA1）与早发型子痫前期（EOPE）的关系，并确定 FOXA1 对滋养细胞凋亡、迁移和侵袭的影响。
收集海南医学院第一附属医院 EOPE 患者和正常孕妇的临床资料和胎盘。采用 Western blot 和免疫组织化学法检测临床标本中 FOXA1 的蛋白表达水平。通过流式细胞术、划痕愈合和 Transwell 侵袭实验分别评估 FOXA1 敲低对 HTR-8/SVneo 细胞凋亡、迁移和侵袭的影响。
Western blot 和免疫组化分析显示，EOPE 组胎盘 FOXA1 蛋白表达明显低于正常组。EOPE 和正常孕妇胎盘 FOXA1 的表达与收缩压和舒张压呈负相关。EOPE 和正常孕妇胎盘 FOXA1 的表达与分娩时的孕周和新生儿出生体重呈正相关。体外功能研究表明，沉默 FOXA1 可增加细胞凋亡，抑制 HTR-8/SVneo 细胞的迁移和侵袭。
胎盘 FOXA1 的下调可能预示着 EOPE 的不良预后。FOXA1 的沉默诱导滋养细胞凋亡，并损害滋养细胞的迁移和侵袭能力。FOXA1 可能是 EOPE 的潜在治疗靶点。
