Marie Austdal1, Liv Cecilie Vestrheim Thomsen2, Line Haugstad Tangerås3, Bente Skei4, Seema Mathew5, Line Bjørge6, Rigmor Austgulen7, Tone Frost Bathen8, Ann-Charlotte Iversen9. 1. 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. 2. 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. 3. 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. 4. Centre of Molecular Inflammation Research, and Department of Cancer Research and Molecular Medicine, NTNU, 7491 Trondheim, Norway. Electronic address: bente.skei@ntnu.no. 5. Department of Gynecology and Obstetrics, Haukeland University Hospital, 5021 Bergen, Norway. Electronic address: seemamathew.sm@gmail.com. 6. 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. 7. Centre of Molecular Inflammation Research, and Department of Cancer Research and Molecular Medicine, NTNU, 7491 Trondheim, Norway. Electronic address: rigmor.austgulen@ntnu.no. 8. 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. 9. Centre of Molecular Inflammation Research, and Department of Cancer Research and Molecular Medicine, NTNU, 7491 Trondheim, Norway. Electronic address: ann-charlotte.iversen@ntnu.no.
Abstract
INTRODUCTION: 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. DISCUSSION: 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.
INTRODUCTION: 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. DISCUSSION: 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: Ralph McGinnis; Valgerdur Steinthorsdottir; Nicholas O Williams; Gudmar Thorleifsson; Scott Shooter; Sigrun Hjartardottir; Suzannah Bumpstead; Lilja Stefansdottir; Lucy Hildyard; Jon K Sigurdsson; John P Kemp; Gabriela B Silva; Liv Cecilie V Thomsen; Tiina Jääskeläinen; Eero Kajantie; Sally Chappell; Noor Kalsheker; Ashley Moffett; Susan Hiby; Wai Kwong Lee; Sandosh Padmanabhan; Nigel A B Simpson; Vivien A Dolby; Eleonora Staines-Urias; Stephanie M Engel; Anita Haugan; Lill Trogstad; Gulnara Svyatova; Nodira Zakhidova; Dilbar Najmutdinova; Anna F Dominiczak; Håkon K Gjessing; Juan P Casas; Frank Dudbridge; James J Walker; Fiona Broughton Pipkin; Unnur Thorsteinsdottir; Reynir T Geirsson; Debbie A Lawlor; Ann-Charlotte Iversen; Per Magnus; Hannele Laivuori; Kari Stefansson; Linda Morgan Journal: Nat Genet Date: 2017-06-19 Impact factor: 38.330
Authors: Rachel S Kelly; Rachel T Giorgio; Bo L Chawes; Natalia I Palacios; Kathryn J Gray; Hoooman Mirzakhani; Ann Wu; Kevin Blighe; Scott T Weiss; Jessica Lasky-Su Journal: Metabolomics Date: 2017-06-12 Impact factor: 4.290
Authors: Julia H King; Sze Ting Cecilia Kwan; Jian Yan; Kevin C Klatt; Xinyin Jiang; Mark S Roberson; Marie A Caudill Journal: Nutrients Date: 2017-07-18 Impact factor: 5.717