title: Dynamics of Base Excision Repair at the Maternal-Fetal Interface in Pregnancies Complicated by Preeclampsia.
abstract: Preeclampsia (PE) (gestational proteinuric hypertension) is the leading cause of maternal and perinatal mortality worldwide. Although placental endothelial dysfunction and oxidative stress are known to contribute to PE, the exact pathological basis for this disorder remains unclear. Previously, we demonstrated that DNA damage at the maternal-fetal interface is more common in the placentas of women with PE than normotensive controls. In this study, we utilized an in vivo comparative study, including 20 preeclamptic women and 8 healthy control subjects, and an in vitro hypoxia/reperfusion model to mimic the effects of oxidative stress at the maternal-fetal interface. We tracked the spatial pattern of expression of 2 base excision repair proteins, 8-oxoguanine glycosylase (OGG1) and apurinic/apyrimidinic endonuclease-1 (APE1), at the maternal-fetal interface in response to oxidative stress. In vivo, we found a significant increase in OGG1 and APE1 concentrations in PE placental tissues as compared to normotensive controls ( P < .0001). Further, our in vitro study revealed that OGG1 and APE1 expression is much greater in maternal cells (decidua) than in fetal cells (cytotrophoblasts) of placental tissue subjected to oxidative stress ( P < .0001). Our results suggest that OGG1 and APE1 likely protect decidual cells from oxidative base damage.
authors.affiliation: 1 Department of Obstetrics and Gynecology, Tufts University School of Medicine, Boston, MA, USA.|2 Mother Infant Research Institute, Tufts Medical Center, Boston, MA, USA.
authors.forename: Serkalem
authors.initials: S
authors.lastname: Tadesse
authors.affiliation: 3 Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Norwitz
authors.affiliation: 3 Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Seth
authors.initials: S
authors.lastname: Guller
authors.affiliation: 4 Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Arcuri
authors.affiliation: 5 Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Toti
authors.affiliation: 1 Department of Obstetrics and Gynecology, Tufts University School of Medicine, Boston, MA, USA.|2 Mother Infant Research Institute, Tufts Medical Center, Boston, MA, USA.
authors.forename: Errol R
authors.initials: ER
authors.lastname: Norwitz
authors.affiliation: 6 Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, Austin, TX, USA.
authors.forename: Dawit
authors.initials: D
authors.lastname: Kidane
mesh_terms: D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D018384:Oxidative Stress / Q000235:genetics*; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism
chemical_list: D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
keywords: OGG1 and APE1; base excision repair; preeclampsia