title: The severity of hypoxic changes and oxidative DNA damage in the placenta of early-onset preeclamptic women and fetal growth restriction.
abstract: OBJECTIVE
  To investigate the relation between the severity of hypoxic changes and oxidative DNA damage in the placenta of early and late-onset preeclampic women and fetal growth restriction (FGR), serum parameters of oxidative stress, placental hypoxic change, and oxidative DNA damage were determined.
  
  
  METHODS
  We examined 10 participants with uncomplicated pregnancies, 13 with early-onset and 12 with late-onset preeclampsia. Maternal and umbilical plasma derivatives of reactive oxygen metabolites (d-ROMs) were measured as markers of oxygen free radicals. Immunohistochemical analysis was performed to measure the proportion of placental trophoblast cell nuclei staining positive for 8-hydroxy-2'-deoxyguanosine (8-OHdG), redox factor-1 (ref-1), and hypoxia-induced factor-1α (HIF-1α), which are markers of oxidative DNA damage, repair functions, and hypoxia status, respectively.
  
  
  RESULTS
  8-OHdG was higher in both preeclamptic groups, but significantly higher in the early-onset preeclamptic group. Ref-1 was higher in the late-onset preeclamptic group. HIF-1α was higher in both preeclamptic groups, with a tendency towards a higher in the early-onset preeclamptic group.
  
  
  CONCLUSIONS
  Our findings indicate that the severity of hypoxic changes and oxidative DNA damage are greater in the placenta of women with early-onset preeclampsia, and that the prolonged preeclamptic conditions may reduce placental blood flow, ultimately leading to FGR.
authors.affiliation: Department of Obstetrics and Gynecology, Aichi Medical University School of Medicine, Aichi, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kimura
authors.forename: Kazushi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Ai
authors.initials: A
authors.lastname: Iwasaki
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Mori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsushita
authors.forename: Koichi
authors.initials: K
authors.lastname: Shinohara
authors.forename: Akihiko
authors.initials: A
authors.lastname: Wakatsuki
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D015687:Cell Hypoxia; D004249:DNA Damage / Q000502:physiology*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000032:analysis; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D005260:Female; D005317:Fetal Growth Retardation / Q000473:pathology / Q000503:physiopathology*; D005865:Gestational Age; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D007150:Immunohistochemistry; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010920:Placenta / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D011225:Pre-Eclampsia / Q000473:pathology / Q000503:physiopathology*; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000097:blood; D014469:Umbilical Arteries
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D003849:Deoxyguanosine