title: Endothelin-1 triggers placental oxidative stress pathways: putative role in preeclampsia.
abstract: BACKGROUND
  Preeclampsia (PE) is a disorder that occurs only during pregnancy. The placenta has a controlling role in this condition. Recent literature suggests that the oxidative stress is a component of PE and plays a main role in the link between decreased placental perfusion and the impaired function of maternal endothelium.
  
  
  OBJECTIVE
  Because the human placenta expresses endothelin-1 (ET-1) and its circulating levels are high in pregnancies complicated with PE, the present study investigated the role of ET-1 on placental oxidative stress pathways.
  
  
  METHODS
  Human placental explants, JEG-3, and primary cytotrophoblast cells were cultured with increasing ET-1 concentrations for 6 and 24 h.
  
  
  METHODS
  The study was conducted at tertiary clinical care centers in Siena and Padova, Italy.
  
  
  METHODS
  Human placental explants, JEG-3, and primary cytotrophoblast cells were used to test ET-1 effect.
  
  
  METHODS
  The main outcome measure was ET-1 mRNA and its receptor mRNAs, type A and B, detection by RT-PCR. The common markers of oxidative stress [malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), ascorbic acid (AA)] as well as cell proliferation and vitality were measured after stimulation periods.
  
  
  RESULTS
  ET-1 inhibits cell proliferation and vitality and triggers oxidative stress in the human placenta by altering the balance between oxidant (increased MDA levels) and antioxidant (decreased GSH, GSSG, and AA) forces in favor of oxidation.
  
  
  CONCLUSIONS
  Because MDA damages endothelial cells, whereas GSH, GSSG, and AA protect them, we postulate that ET-1 may be one of the key links between primary placental disorders and the systemic endothelial dysfunction of PE.
authors.affiliation: Department of Obstetrics and Gynecology, Giorgio Segre, University of Siena, Siena, Italy.
authors.forename: Giovina
authors.initials: G
authors.lastname: Fiore
authors.forename: Pasquale
authors.initials: P
authors.lastname: Florio
authors.forename: Lucia
authors.initials: L
authors.lastname: Micheli
authors.forename: Cristina
authors.initials: C
authors.lastname: Nencini
authors.forename: Marco
authors.initials: M
authors.lastname: Rossi
authors.forename: Daniela
authors.initials: D
authors.lastname: Cerretani
authors.forename: Guido
authors.initials: G
authors.lastname: Ambrosini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giorgi
authors.forename: Felice
authors.initials: F
authors.lastname: Petraglia
mesh_terms: D045744:Cell Line, Tumor; D019332:Endothelin-1 / Q000502:physiology*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D018384:Oxidative Stress; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000209:etiology*; D011247:Pregnancy
chemical_list: D019332:Endothelin-1; D005978:Glutathione