title: Metabolic targets of endocrine disrupting chemicals assessed by cord blood transcriptome profiling.
abstract: Early life exposure to endocrine disrupting chemicals (EDCs) has been frequently associated with impaired perinatal growth, an important risk factor for later onset of metabolic disorders. We analyzed whether the cord blood transcriptome showed early indications of alterations in metabolic processes in 195 human samples in relation to cord blood levels of dichlorodiphenyldichloroethylene (p,p'-DDE), polychlorinated biphenyl-153 (PCB-153), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonate (PFOS). Overall, 39 metabolically relevant transcription factors were significantly enriched (31 by p,p'-DDE, 10 by PCB-153, 8 by PFOA, and 2 by PFOS). These included the glucocorticoid receptor (p,p'-DDE and PCB-153) and the progesterone receptor (PFOA and PFOS). The 'insulin receptor signaling', 'acute phase response signaling', 'Interleukin(IL)-6 signaling', and 'prolactin signaling' pathways were significantly enriched in relation to p,p'-DDE. Transcriptional changes at birth suggest a role for specific metabolic targets as a link between prenatal EDC exposure and metabolic disorders later in life.
authors: Epidemiology and Social Medicine, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium; Environmental Risk and Health, Flemish Institute for Technological Research (VITO), Boeretang 200, 2400, Mol, Belgium. Electronic address: sylvie.remy@uantwerpen.be.
authors: Sylvie
authors: S
authors: Remy
authors: Environmental Risk and Health, Flemish Institute for Technological Research (VITO), Boeretang 200, 2400, Mol, Belgium.
authors: Eva
authors: E
authors: Govarts
authors: Environmental Risk and Health, Flemish Institute for Technological Research (VITO), Boeretang 200, 2400, Mol, Belgium.
authors: Britt
authors: B
authors: Wens
authors: Environmental Risk and Health, Flemish Institute for Technological Research (VITO), Boeretang 200, 2400, Mol, Belgium; Centre for Environmental Sciences, Hasselt University, Agoralaan gebouw D, 3590, Diepenbeek, Belgium.
authors: Patrick
authors: P
authors: De Boever
authors: Environmental Risk and Health, Flemish Institute for Technological Research (VITO), Boeretang 200, 2400, Mol, Belgium; Directorate of Public Health and Surveillance, Scientific Institute of Public Health, Juliette Wytsmanstraat 14, 1050, Brussels, Belgium.
authors: Elly
authors: E
authors: Den Hond
authors: Department of Analytical, Environmental and Geochemistry (AEGC), Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium.
authors: Kim
authors: K
authors: Croes
authors: Department of Public Health, Ghent University, St. Pietersnieuwstraat 33, 9000, Ghent, Belgium; FWO Research Foundation, Egmontstraat 5, 1000, Brussels, Belgium.
authors: Isabelle
authors: I
authors: Sioen
authors: Department of Analytical, Environmental and Geochemistry (AEGC), Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium.
authors: Willy
authors: W
authors: Baeyens
authors: Department of Analytical, Environmental and Geochemistry (AEGC), Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium; Department of Radiotherapy and Experimental cancer research, Ghent University, St. Pietersnieuwstraat 33, 9000, Ghent, Belgium.
authors: Nicolas
authors: N
authors: van Larebeke
authors: EKZ-AMC, University of Amsterdam, De Boelelaan 1105, 1081 HV, Amsterdam, The Netherlands.
authors: Janna
authors: J
authors: Koppe
authors: Toxicological Center, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium.
authors: Adrian
authors: A
authors: Covaci
authors: Institute for Occupational and Social Medicine, Medical Faculty, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
authors: Thomas
authors: T
authors: Schettgen
authors: Department of Health, Provincial Institute for Hygiene, Kronenburgstraat 45, 2000, Antwerp, Belgium.
authors: Vera
authors: V
authors: Nelen
authors: Institute for Environmental Studies, VU University Amsterdam, De Boelelaan 1105, 1081 HV Amsterdam, The Netherlands.
authors: Juliette
authors: J
authors: Legler
authors: Environmental Risk and Health, Flemish Institute for Technological Research (VITO), Boeretang 200, 2400, Mol, Belgium; Biomedical Sciences, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium; Environmental Medicine, University of Southern Denmark, Odense, Campusvej 55, 5000, Odense, Denmark.
authors: Greet
authors: G
authors: Schoeters
mesh_terms: D000328:Adult; D001151:Arsenic / Q000097:blood; D001530:Belgium; D052244:Endocrine Disruptors / Q000097:blood*; D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000097:blood*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D005466:Fluorocarbons / Q000097:blood; D020869:Gene Expression Profiling; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000097:blood; D007231:Infant, Newborn; D008297:Male; D019216:Metals, Heavy / Q000097:blood; D010795:Phthalic Acids / Q000097:blood; D011247:Pregnancy
chemical_list: D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D005466:Fluorocarbons; D006843:Hydrocarbons, Chlorinated; D019216:Metals, Heavy; D010795:Phthalic Acids; D001151:Arsenic
keywords: Birth cohort; Cord blood; Endocrine disrupting chemicals; Glucocorticoid receptor; Metabolic disorders; Transcriptomics