title: Glucocorticoid exposure in early placentation induces preeclampsia in rats via interfering trophoblast development.
abstract: 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.
authors.affiliation: 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.
authors.forename: Dongxin
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, People's Republic of China.
authors.forename: Haojing
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, People's Republic of China.
authors.forename: Ji
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Clinical Laboratory, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, People's Republic of China.
authors.forename: Xili
authors.initials: X
authors.lastname: Miao
authors.affiliation: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Gynecology and Obstetrics, First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325003, People's Republic of China.
authors.forename: Yinping
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China. Electronic address: yedy@mails.tjmu.edu.cn.
authors.forename: Duyun
authors.initials: D
authors.lastname: Ye
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010929:Placentation / Q000187:drug effects*; D011225:Pre-Eclampsia / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D005938:Glucocorticoids; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D003907:Dexamethasone
keywords: Epithelial–mesenchymal transition; Glucocorticoid; Placentation; Preeclampsia; Trophoblast development