title: The effects of Nrf2 deletion on placental morphology and exchange capacity in the mouse.
abstract: OBJECTIVE
  Intrauterine growth restriction (IUGR) is defined as a pathological decreased fetal growth. Oxidative stress has been connected to the restriction in the fetal growth. The transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) is a potent activator of the cellular antioxidant response. The effect Nrf2 on fetal-placental development has not yet been sufficiently investigated. Here, we evaluated the placental and fetal growth in Nrf2 knockout (Nrf2-KO) and Nrf2-wild type mice (Nrf2-WT) throughout pregnancy.
  
  
  METHODS
  Heterozygote Nrf2 (Nrf2+/-) mice were paired to get Nrf2-KO and Nrf2-WT in the litters. Placentae and embryos from both genotypes were collected and weighed on days 13.5, 15.5 and 18.5 post coitum. The absolute volumes of the labyrinth zone and the total volume of the placenta were determined using the Cavalieri principle.
  
  
  RESULTS
  On E 18.5 the fetal weight in Nrf2-KO was significantly reduced versus Nrf2-WT indicating a decrease in placental efficiency. A significant reduction in both total and labyrinth-volume in the placenta of Nrf2-KO mice was observed.
  
  
  CONCLUSIONS
  This data points out the necessity of functional Nrf2 for fetal and placental growth. A deficiency in Nrf2 signaling may negatively affect nutrient transfer capacity which is then no longer able to meet fetal growth demands.
authors.affiliation: a Department of Anatomy and Cell Biology , RWTH Aachen University Hospital , Aachen , Germany.
authors.forename: Nisreen
authors.initials: N
authors.lastname: Kweider
authors.affiliation: b Institute of Cell Biology, Histology & Embryology, Medical University of Graz , Graz , Austria.
authors.forename: Berthold
authors.initials: B
authors.lastname: Huppertz
authors.affiliation: c Faculty of Medicine , Gynecology and Obstetrics, RWTH Aachen University Hospital , Aachen , Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Rath
authors.affiliation: d Institut of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH Aachen University Hospital , Aachen , Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Lambertz
authors.affiliation: e Department of Obstetrics and Gynecology , RWTH Aachen University Hospital , Aachen , Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Caspers
authors.affiliation: f Section of Obstetrics and Gynecology, Leeds Institute of Biomedical and Clinical sciences, University of Leeds , Leeds , UK.|g Department of Obstetrics and Gynecology , Mansoura University Faculty of Medicine , Mansoura , Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: ElMoursi
authors.affiliation: e Department of Obstetrics and Gynecology , RWTH Aachen University Hospital , Aachen , Germany.|h Department of Obstetrics and Gynecology , University Hospital Schleswig-Holstein , Kiel , Germany , and.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pecks
authors.affiliation: a Department of Anatomy and Cell Biology , RWTH Aachen University Hospital , Aachen , Germany.|i Department of Neurology Mittelbaden Klinikum Baden-Baden , Baden-Baden , Germany.
authors.forename: Mamed
authors.initials: M
authors.lastname: Kadyrov
authors.affiliation: a Department of Anatomy and Cell Biology , RWTH Aachen University Hospital , Aachen , Germany.
authors.forename: Athanassios
authors.initials: A
authors.lastname: Fragoulis
authors.affiliation: a Department of Anatomy and Cell Biology , RWTH Aachen University Hospital , Aachen , Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pufe
authors.affiliation: a Department of Anatomy and Cell Biology , RWTH Aachen University Hospital , Aachen , Germany.
authors.forename: Christoph Jan
authors.initials: CJ
authors.lastname: Wruck
mesh_terms: D000818:Animals; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D005317:Fetal Growth Retardation / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D010929:Placentation / Q000502:physiology*; D011247:Pregnancy
chemical_list: D051267:NF-E2-Related Factor 2
keywords: IUGR; Nrf2; oxidative stress; placenta; placental insufficiency