title: Cord blood gene expression supports that prenatal exposure to perfluoroalkyl substances causes depressed immune functionality in early childhood.
abstract: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a class of synthetic compounds that have widespread use in consumer and industrial applications. PFAS are considered environmental pollutants that have various toxic properties, including effects on the immune system. Recent human studies indicate that prenatal exposure to PFAS leads to suppressed immune responses in early childhood. In this study, data from the Norwegian BraMat cohort was used to investigate transcriptomics profiles in neonatal cord blood and their association with maternal PFAS exposure, anti-rubella antibody levels at 3 years of age and the number of common cold episodes until 3 years. Genes associated with PFAS exposure showed enrichment for immunological and developmental functions. The analyses identified a toxicogenomics profile of 52 PFAS exposure-associated genes that were in common with genes associated with rubella titers and/or common cold episodes. This gene set contains several immunomodulatory genes (CYTL1, IL27) as well as other immune-associated genes (e.g. EMR4P, SHC4, ADORA2A). In addition, this study identified PPARD as a PFAS toxicogenomics marker. These markers can serve as the basis for further mechanistic or epidemiological studies. This study provides a transcriptomics connection between prenatal PFAS exposure and impaired immune function in early childhood and supports current views on PPAR- and NF-κB-mediated modes of action. The findings add to the available evidence that PFAS exposure is immunotoxic in humans and support regulatory policies to phase out these substances.
authors: a Centre for Health Protection, National Institute for Public Health and the Environment (RIVM) , Bilthoven , the Netherlands .
authors: Jeroen L A
authors: JL
authors: Pennings
authors: b Department of Toxicogenomics , Maastricht University , Maastricht , the Netherlands , and.
authors: Danyel G J
authors: DG
authors: Jennen
authors: c Division of Environmental Medicine , Norwegian Institute of Public Health (NIPH) , Oslo , Norway.
authors: Unni C
authors: UC
authors: Nygaard
authors: c Division of Environmental Medicine , Norwegian Institute of Public Health (NIPH) , Oslo , Norway.
authors: Ellen
authors: E
authors: Namork
authors: c Division of Environmental Medicine , Norwegian Institute of Public Health (NIPH) , Oslo , Norway.
authors: Line S
authors: LS
authors: Haug
authors: a Centre for Health Protection, National Institute for Public Health and the Environment (RIVM) , Bilthoven , the Netherlands .|b Department of Toxicogenomics , Maastricht University , Maastricht , the Netherlands , and.
authors: Henk
authors: H
authors: van Loveren
authors: c Division of Environmental Medicine , Norwegian Institute of Public Health (NIPH) , Oslo , Norway.
authors: Berit
authors: B
authors: Granum
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology*; D002675:Child, Preschool; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D005466:Fluorocarbons / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology* / Q000473:pathology; D012409:Rubella / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D005466:Fluorocarbons; C040901:rubella antibodies
keywords: Immunotoxicity; perfluoroalkyl carboxylic acids; perfluoroalkyl substances; perfluoroalkyl sulfonic acids; prenatal exposure; toxicogenomics