Glucocorticoid exposure in early placentation induces preeclampsia in rats via interfering trophoblast development

• Glucocorticoid (GC) exposure in early placentation induces preeclampsia (PE) in rats.
• GC inhibits trophoblast development both in vivo and in vitro.
• GC exposure leads to rat PE partially via inhibiting trophoblast invasion and EMT.
• GC receptor and ERK are involved in the inhibition of GC on trophoblast development.

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 2.5 mg/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.