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.

• Immunotoxicity
• perfluoroalkyl carboxylic acids
• perfluoroalkyl substances
• perfluoroalkyl sulfonic acids
• prenatal exposure
• toxicogenomics

Acknowledgments

The authors are grateful to all the participating families in Norway who took part in the BraMat study. The authors thank the technicians Bodil Hasseltvedt, Else-Carin Groeng, Astri Grestad, Berit Arvesen Stensby, Åse Eikeset, Azemira Sabaredzovic, Anne-Cathrine Kristoffersen, Dr Solvor Berntsen Stølevik, Dr Ingeborg S Aaberge and Dr Kirsti Vainio at the Norwegian Institute of Public Health for their assistance in the project. The authors are also grateful to the staff at the maternity wards and laboratories at Oslo and Akershus University Hospitals for their contribution to the recruitment of participants and assistance in blood sampling and processing.

Declaration of interest

The authors report no conflicts of interest. This project was supported by the Research Council of Norway [grant number 228195/H10]. Part of this work was supported by the European Union 6th Framework Programme (Integrated Project NewGeneris [FOOD-CT-2005-016320]) and the Norwegian Institute of Public Health. The authors alone are responsible for the content and writing of the paper.

Supplementary material available online Supplementary Tables 1–3