The severity of hypoxic changes and oxidative DNA damage in the placenta of early-onset preeclamptic women and fetal growth restriction

J Matern Fetal Neonatal Med. 2013 Mar;26(5):491-6. doi: 10.3109/14767058.2012.733766. Epub 2012 Nov 8.

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.

Publication types

  • Comparative Study

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adult
  • Cell Hypoxia
  • DNA Damage / physiology*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / analysis
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / analysis
  • Female
  • Fetal Growth Retardation / pathology
  • Fetal Growth Retardation / physiopathology*
  • Gestational Age
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / analysis
  • Immunohistochemistry
  • Oxidation-Reduction
  • Oxidative Stress
  • Placenta / chemistry
  • Placenta / pathology
  • Placenta / physiopathology*
  • Pre-Eclampsia / pathology
  • Pre-Eclampsia / physiopathology*
  • Pregnancy
  • Reactive Oxygen Species / blood
  • Umbilical Arteries

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Reactive Oxygen Species
  • 8-Hydroxy-2'-Deoxyguanosine
  • APEX1 protein, human
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • Deoxyguanosine