title: Metabolic profiles of placenta in preeclampsia using HR-MAS MRS metabolomics.
abstract: BACKGROUND
  Preeclampsia is a heterogeneous gestational disease characterized by maternal hypertension and proteinuria, affecting 2-7% of pregnancies. The disorder is initiated by insufficient placental development, but studies characterizing the placental disease components are lacking.
  
  
  METHODS
  Our aim was to phenotype the preeclamptic placenta using high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MAS MRS). Placental samples collected after delivery from women with preeclampsia (n = 19) and normotensive pregnancies (n = 15) were analyzed for metabolic biomarkers including amino acids, osmolytes, and components of the energy and phospholipid metabolism. The metabolic biomarkers were correlated to clinical characteristics and inflammatory biomarkers in the maternal sera.
  
  
  RESULTS
  Principal component analysis showed inherent differences in placental metabolic profiles between preeclamptic and normotensive pregnancies. Significant differences in metabolic profiles were found between placentas from severe and non-severe preeclampsia, but not between preeclamptic pregnancies with fetal growth restricted versus normal weight neonates. The placental metabolites correlated with the placental stress marker sFlt-1 and triglycerides in maternal serum, suggesting variation in placental stress signaling between different placental phenotypes.
  
  
  CONCLUSIONS
  HR-MAS MRS is a sensitive method for defining the placental disease component of preeclampsia, identifying several altered metabolic pathways. Placental HR-MAS MRS analysis may improve insight into processes affected in the preeclamptic placenta, and represents a novel long-required tool for a sensitive placental phenotyping of this heterogeneous disease.
authors.affiliation: Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway; St. Olavs Hospital, Trondheim University Hospital, 7006 Trondheim, Norway; Centre of Molecular Inflammation Research, and Department of Cancer Research and Molecular Medicine, NTNU, 7491 Trondheim, Norway. Electronic address: marie.austdal@ntnu.no.
authors.forename: Marie
authors.initials: M
authors.lastname: Austdal
authors.affiliation: Department of Gynecology and Obstetrics, Haukeland University Hospital, 5021 Bergen, Norway; Department of Clinical Science, University of Bergen, 5021 Bergen, Norway; Centre of Molecular Inflammation Research, and Department of Cancer Research and Molecular Medicine, NTNU, 7491 Trondheim, Norway. Electronic address: liv.vestrheim@uib.no.
authors.forename: Liv Cecilie Vestrheim
authors.initials: LC
authors.lastname: Thomsen
authors.affiliation: St. Olavs Hospital, Trondheim University Hospital, 7006 Trondheim, Norway; Centre of Molecular Inflammation Research, and Department of Cancer Research and Molecular Medicine, NTNU, 7491 Trondheim, Norway. Electronic address: line.tangeraas@gmail.com.
authors.forename: Line Haugstad
authors.initials: LH
authors.lastname: Tangerås
authors.affiliation: Centre of Molecular Inflammation Research, and Department of Cancer Research and Molecular Medicine, NTNU, 7491 Trondheim, Norway. Electronic address: bente.skei@ntnu.no.
authors.forename: Bente
authors.initials: B
authors.lastname: Skei
authors.affiliation: Department of Gynecology and Obstetrics, Haukeland University Hospital, 5021 Bergen, Norway. Electronic address: seemamathew.sm@gmail.com.
authors.forename: Seema
authors.initials: S
authors.lastname: Mathew
authors.affiliation: Department of Gynecology and Obstetrics, Haukeland University Hospital, 5021 Bergen, Norway; Department of Clinical Science, University of Bergen, 5021 Bergen, Norway. Electronic address: line.bjorge@uib.no.
authors.forename: Line
authors.initials: L
authors.lastname: Bjørge
authors.affiliation: Centre of Molecular Inflammation Research, and Department of Cancer Research and Molecular Medicine, NTNU, 7491 Trondheim, Norway. Electronic address: rigmor.austgulen@ntnu.no.
authors.forename: Rigmor
authors.initials: R
authors.lastname: Austgulen
authors.affiliation: Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway. Electronic address: tone.f.bathen@ntnu.no.
authors.forename: Tone Frost
authors.initials: TF
authors.lastname: Bathen
authors.affiliation: Centre of Molecular Inflammation Research, and Department of Cancer Research and Molecular Medicine, NTNU, 7491 Trondheim, Norway. Electronic address: ann-charlotte.iversen@ntnu.no.
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Iversen
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome / Q000502:physiology*; D055432:Metabolomics; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D055815:Young Adult
keywords: Metabolism; Metabolomics; NMR; Placenta; Preeclampsia; Profiling