title: Maternal Pre-Pregnancy Obesity Is Associated with Altered Placental Transcriptome.
abstract: Maternal obesity has a major impact on pregnancy outcomes. There is growing evidence that maternal obesity has a negative influence on placental development and function, thereby adversely influencing offspring programming and health outcomes. However, the molecular mechanisms underlying these processes are poorly understood. We analysed ten term placenta's whole transcriptomes in obese (n = 5) and normal weight women (n = 5), using the Affymetrix microarray platform. Analyses of expression data were carried out using non-parametric methods. Hierarchical clustering and principal component analysis showed a clear distinction in placental transcriptome between obese and normal weight women. We identified 72 differentially regulated genes, with most being down-regulated in obesity (n = 61). Functional analyses of the targets using DAVID and IPA confirm the dysregulation of previously identified processes and pathways in the placenta from obese women, including inflammation and immune responses, lipid metabolism, cancer pathways, and angiogenesis. In addition, we detected new molecular aspects of obesity-derived effects on the placenta, involving the glucocorticoid receptor signalling pathway and dysregulation of several genes including CCL2, FSTL3, IGFBP1, MMP12, PRG2, PRL, QSOX1, SERPINE2 and TAC3. Our global gene expression profiling approach demonstrates that maternal obesity creates a unique in utero environment that impairs the placental transcriptome.
authors.affiliation: Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet, Stockholm, Sweden.|Centre of Excellence for Paediatric Research EURISTIKOS and Department of Paediatrics, School of Medicine, University of Granada, Granada, Spain.
authors.forename: Signe
authors.identifier: http://orcid.org/0000-0002-0708-1865
authors.initials: S
authors.lastname: Altmäe
authors.affiliation: Centre of Excellence for Paediatric Research EURISTIKOS and Department of Paediatrics, School of Medicine, University of Granada, Granada, Spain.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Segura
authors.affiliation: Department of Experimental Biology, University of Jaén, Jaén, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Esteban
authors.affiliation: Division of Experimental Asthma Research, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Member of the German Center for Lung Research (DZL), Borstel, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Bartel
authors.affiliation: Centre of Excellence for Paediatric Research EURISTIKOS and Department of Paediatrics, School of Medicine, University of Granada, Granada, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Brandi
authors.affiliation: Institute of Experimental Genetics, Helmholtz Zentrum Muenchen, Neuherberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Irmler
authors.affiliation: Institute of Experimental Genetics, Helmholtz Zentrum Muenchen, Neuherberg, Germany.|Technische Universität München, Chair of Experimental Genetics, Freising, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Beckers
authors.affiliation: Ludwig-Maximilians-University of Munich, Dr. Hauner Children's Hospital, University of Munich Medical Centre, Munich, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Demmelmair
authors.affiliation: Department of Nutrition and Bromatology, School of Pharmacy, University of Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: López-Sabater
authors.affiliation: Ludwig-Maximilians-University of Munich, Dr. Hauner Children's Hospital, University of Munich Medical Centre, Munich, Germany.
authors.forename: Berthold
authors.initials: B
authors.lastname: Koletzko
authors.affiliation: Division of Experimental Asthma Research, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Member of the German Center for Lung Research (DZL), Borstel, Germany.|Institute for Experimental Medicine, Christian-Albrechts-Universitaet zu Kiel, Kiel, Germany.|Comprehensive Pneumology Center, Ludwig Maximilians University Hospital and Helmholtz Zentrum München, Großhadern, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Krauss-Etschmann
authors.affiliation: Centre of Excellence for Paediatric Research EURISTIKOS and Department of Paediatrics, School of Medicine, University of Granada, Granada, Spain.|Biohealth Institute of Granada, Granada, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Campoy
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D007249:Inflammation; D050356:Lipid Metabolism / Q000235:genetics / Q000276:immunology; D046228:Microarray Analysis; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000276:immunology / Q000473:pathology; D009765:Obesity / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D010920:Placenta / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010929:Placentation / Q000235:genetics* / Q000276:immunology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics* / Q000276:immunology; D025341:Principal Component Analysis; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000276:immunology; D059467:Transcriptome
chemical_list: D009363:Neoplasm Proteins; D011965:Receptors, Glucocorticoid