title: The impact of ionizing radiation on placental trophoblasts.
abstract: BACKGROUND
  Exposure to low-dose radiation is widespread and attributable to natural sources. However, occupational, medical, accidental, and terrorist-related exposures remain a significant threat. Information on radiation injury to the feto-placental unit is scant and largely observational. We hypothesized that radiation causes trophoblast injury, and alters the expression of injury-related transcripts in vitro or in vivo, thus affecting fetal growth.
  
  
  METHODS
  Primary human trophoblasts (PHTs), BeWo or NCCIT cells were irradiated in vitro, and cell number and viability were determined. Pregnant C57Bl/6HNsd mice were externally irradiated on E13.5, and placentas examined on E17.5. RNA expression was analyzed using microarrays and RT-qPCR. The experiments were repeated in the presence of the gramicidin S (GS)-derived nitroxide JP4-039, used to mitigate radiation-induced cell injury.
  
  
  RESULTS
  We found that survival of in vitro-irradiated PHT cell was better than that of irradiated BeWo trophoblast cell line or the radiosensitive NCCIT mixed germ cell tumor line. Radiation altered the expression of several trophoblast genes, with a most dramatic effect on CDKN1A (p21, CIP1). Mice exposed to radiation at E13.5 exhibited a 25% reduction in mean weight by E17.5, and a 9% reduction in placental weight, which was associated with relatively small changes in placental gene expression. JP4-039 had a minimal effect on feto-placental growth or on gene expression in irradiated PHT cells or mouse placenta.
  
  
  CONCLUSIONS
  While radiation affects placental trophoblasts, the established placenta is fairly resistant to radiation, and changes in this tissue may not fully account for fetal growth restriction induced by ionizing radiation.
authors.affiliation: Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Kanter
authors.affiliation: Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: O'Brien
authors.affiliation: Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: X-H
authors.initials: XH
authors.lastname: Shi
authors.affiliation: Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Chu
authors.affiliation: Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Mishima
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Beriwal
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Epperly
authors.affiliation: Department of Chemistry and the Center for Chemical Methodologies and Library Development, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Wipf
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Greenberger
authors.affiliation: Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: ysadovsky@mwri.magee.edu.
authors.forename: Y
authors.initials: Y
authors.lastname: Sadovsky
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D047109:Fetal Development / Q000528:radiation effects*; D005317:Fetal Growth Retardation / Q000209:etiology; D018507:Gene Expression Regulation, Developmental / Q000528:radiation effects*; D006801:Humans; D051379:Mice; D009589:Nitrogen Oxides / Q000627:therapeutic use; D010920:Placenta / Q000528:radiation effects; D011247:Pregnancy; D011832:Radiation Injuries / Q000188:drug therapy; D011839:Radiation, Ionizing; D014327:Trophoblasts / Q000528:radiation effects*; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: C544775:JP4-039; D009589:Nitrogen Oxides
keywords: Ionizing radiation; JP4-039; Microarray; Placenta; Trophoblast