Zhang Dongxin, Liu Haojing, Zeng Ji, Miao Xili, Huang Wei, Chen Hongxiang, Huang Yinping, Li Yongsheng, Ye Duyun
Department of Clinical Laboratory, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, People's Republic of China; Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
Department of Internal Medicine, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, People's Republic of China.
Gen Comp Endocrinol. 2016 Jan 1;225:61-70. doi: 10.1016/j.ygcen.2015.09.019. Epub 2015 Sep 25.
In pregnancy, placenta can be exposed to glucocorticoids (GCs) via several ways, which may disturb placentation and adversely affect pregnancy. Preeclampsia (PE) is thought to be attributed, in part, to impaired trophoblast development. The purpose of the present study was to confirm that GC exposure in early placentation could lead to PE in rats, with the mechanisms involving dysregulated trophoblast development. In the study, pregnant rats were administered with 2.5mg/kg Dex subcutaneously once per day from gestational day 7 to 13. Maternal systolic blood pressure and urinary albumin were increased, while both fetus and placenta were restricted after GC exposure relative to the control group. GC exposure also contributed to placental abnormalities and renal impairment. Moreover, placental oxidative damage was increased along with placental hypoxia-inducible factor 1-alpha (HIF1A) overexpression after GC treatment. Mechanically, GC induced PE in rat partially through inhibiting trophoblast proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), which involved phospho-extracellular signal regulated kinase (p-ERK) downregulation. Furthermore, GC receptor was required for the inhibition of GC on trophoblast proliferation, migration, invasion and EMT in vitro. These findings suggest that GC exposure in early placentation could contribute to PE in pregnant rats, with the mechanisms involving inhibition of trophoblast proliferation, migration, invasion and EMT by GC.
在孕期，胎盘可通过多种途径接触糖皮质激素（GCs），这可能会干扰胎盘形成并对妊娠产生不利影响。子痫前期（PE）被认为部分归因于滋养层发育受损。本研究的目的是证实早期胎盘形成过程中暴露于GCs可导致大鼠发生PE，其机制涉及滋养层发育失调。在该研究中，从妊娠第7天至第13天，每天给孕鼠皮下注射2.5mg/kg地塞米松（Dex）。与对照组相比，GCs暴露后母体收缩压和尿白蛋白增加，而胎儿和胎盘均受限。GCs暴露还导致胎盘异常和肾功能损害。此外，GC处理后胎盘氧化损伤增加，同时胎盘缺氧诱导因子1α（HIF1A）过表达。机制上，GC诱导大鼠发生PE部分是通过抑制滋养层增殖、迁移、侵袭和上皮-间质转化（EMT），这涉及磷酸化细胞外信号调节激酶（p-ERK）下调。此外，体外GC抑制滋养层增殖、迁移、侵袭和EMT需要GC受体。这些发现表明，早期胎盘形成过程中暴露于GCs可导致孕鼠发生PE，其机制包括GC抑制滋养层增殖、迁移、侵袭和EMT。
