title: Excessive autophagy induces the failure of trophoblast invasion and vasculature: possible relevance to the pathogenesis of preeclampsia.
abstract: BACKGROUND
  Preeclampsia affects 5-7% of all healthy pregnancies and is characterized by hypertension and proteinuria. Although the pathogenesis of preeclampsia is still not fully understood, a failure of spiral artery transformation and aberrant placental vasculature are considered to be facets of this disease. Studies have also implicated increased autophagic activity. In this study, we investigated whether oxidative stress could increase autophagic activity and consequently affect trophoblast invasion and the placental vasculature.
  
  
  METHODS
  Placentas from 18 pregnancies complicated by preeclampsia and from 18 uncomplicated pregnancies, trophoblast HTR8/SVneo cell line (HTR8/SVneo) extravillous trophoblasts, and human umbilical vein endothelial cells (HUVECs) were employed. The levels of autophagy markers LC3, Beclin-1 and autophagosome were quantified by immunohistochemistry, Western blotting and RT-PCR in placental tissue, and in trophoblasts and endothelial cells that had been treated with an oxidative stress inducer glucose oxidase. Trophoblast invasion and endothelial cell tube formation were assessed in HTR8/SVneo cells or HUVECs that had been treated with glucose oxidase.
  
  
  RESULTS
  The expression of LC3, Beclin-1 and autophagosome was significantly increased in placentas from pregnancies complicated by early-onset preeclampsia and in HTR8/SVneo cells and HUVECs treated with glucose oxidase. In addition, trophoblast invasion and endothelial cell tube formation were significantly reduced in HTR8/SVneo cells or HUVECs that had been treated with glucose oxidase.
  
  
  CONCLUSIONS
  Our data suggest that oxidative stress induces increased autophagy in trophoblasts or endothelial cells which affects trophoblast invasion and the placental vasculature. Excessive autophagic activity may be involved in the development of preeclampsia.
authors.affiliation: aDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University bCanada-China-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, People's Republic of China cLiggins Institute, University of Auckland, Auckland, New Zealand.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Qi
authors.forename: K C
authors.initials: KC
authors.lastname: Kamana
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Philip N
authors.initials: PN
authors.lastname: Baker
mesh_terms: D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D001343:Autophagy; D000071186:Beclin-1; D002460:Cell Line; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005949:Glucose Oxidase / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D018384:Oxidative Stress; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000503:physiopathology*; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D005949:Glucose Oxidase