title: Oxidative damage and nitric oxide synthase induction by surgical uteroplacental circulation restriction in the rabbit fetal heart.
abstract: OBJECTIVE
  This study investigated the role of oxidative damage and nitric oxide (NO) synthases in the fetal heart using a model of intrauterine growth restriction induced by uteroplacental circulation restriction (UCR).
  
  
  METHODS
  New Zealand white rabbits kept under 12-h light cycles, with food and water provided ad libitum, were subjected at day 25 of pregnancy to 40-50% uteroplacental artery ligation. We analyzed the gene expression of enzymes linked to nitric oxide synthesis (iNOS, eNOS, HO-1, and ARG-2), hypoxia inducible factor 1 alpha (HIF-1α), and the state of oxidative stress (protein carbonyl levels) in fetal heart homogenates. Additionally, we studied the histological morphology of the fetal heart.
  
  
  RESULTS
  We found that fetal growth restriction was associated with a significant reduction in heart weight but a normal heart/body weight ratio in UCR animals. Hematoxylin and eosin staining showed normal left and right ventricular thickness but increased vessel dilatation with hyperemia in the hearts of the UCR group. We observed HIF-1α, eNOS, p-eNOS, and iNOS induction concomitant with intensified protein carbonyl levels but observed no changes in HO-1 or ARG-2 expression, suggesting increased NO and oxidative stress in the hearts of UCR animals.
  
  
  CONCLUSIONS
  Uteroplacental circulation restriction increased NO-linked enzymes, oxidative damage, and dilated coronary vessels in fetal hearts. © 2017 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.
authors.affiliation: Department of Obstetrics and Gynecology and Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de los Andes, Santiago, Chile.|Department of Maternal-Fetal Medicine, Clinica Davila, Santiago, Chile.
authors.forename: Horacio
authors.initials: H
authors.lastname: Figueroa
authors.affiliation: Department of Biological and Chemical Sciences, Universidad San Sebastián, Concepción, Chile.|Faculty of Medicine, Universidad Católica de la Santísima Concepción, Concepción, Chile.
authors.forename: Cristobal
authors.initials: C
authors.lastname: Alvarado
authors.affiliation: Laboratorio de Fisiología Integrativa Molecular, Facultad de Medicina, Universidad de los Andes, Santiago, Chile.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cifuentes
authors.affiliation: Laboratorio de Fisiología Integrativa Molecular, Facultad de Medicina, Universidad de los Andes, Santiago, Chile.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Lozano
authors.affiliation: Laboratorio de Fisiología Integrativa Molecular, Facultad de Medicina, Universidad de los Andes, Santiago, Chile.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Rocco
authors.affiliation: Faculty of Medicine, Universidad Católica de la Santísima Concepción, Concepción, Chile.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cabezas
authors.affiliation: Department of Obstetrics and Gynecology and Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de los Andes, Santiago, Chile.|Department of Maternal-Fetal Medicine, Clinica Davila, Santiago, Chile.
authors.forename: Sebastian E
authors.initials: SE
authors.lastname: Illanes
authors.affiliation: Department of Maternal-Fetal Medicine, Institut Clínic de Ginecologia, Obstetrícia i Neonatologia, and Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain.
authors.forename: Elisenda
authors.initials: E
authors.lastname: Eixarch
authors.affiliation: Department of Maternal-Fetal Medicine, Institut Clínic de Ginecologia, Obstetrícia i Neonatologia, and Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain.|National Institute of Perinatal Medicine, Mexico City, Mexico.
authors.forename: Edgar
authors.initials: E
authors.lastname: Hernández-Andrade
authors.affiliation: Department of Maternal-Fetal Medicine, Institut Clínic de Ginecologia, Obstetrícia i Neonatologia, and Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Gratacós
authors.affiliation: Laboratorio de Fisiología Integrativa Molecular, Facultad de Medicina, Universidad de los Andes, Santiago, Chile.
authors.forename: Carlos E
authors.identifier: http://orcid.org/0000-0002-6538-5314
authors.initials: CE
authors.lastname: Irarrazabal
mesh_terms: D000818:Animals; D003251:Constriction, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D023921:Coronary Stenosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004790:Enzyme Induction; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000473:pathology; D005318:Fetal Heart / Q000378:metabolism* / Q000473:pathology*; D018507:Gene Expression Regulation, Developmental; D019001:Nitric Oxide Synthase / Q000235:genetics*; D018384:Oxidative Stress / Q000502:physiology*; D021041:Placental Circulation; D011247:Pregnancy; D011817:Rabbits
chemical_list: D019001:Nitric Oxide Synthase