Prenatal exposure to perfluoroalkyl substances modulates neonatal serum phospholipids, increasing risk of type 1 diabetes

Aidan McGlinchey; Tim Sinioja; Santosh Lamichhane; Partho Sen; Johanna Bodin; Heli Siljander; Alex M Dickens; Dawei Geng; Cecilia Carlsson; Daniel Duberg; Jorma Ilonen; Suvi M Virtanen; Hubert Dirven; Hanne Friis Berntsen; Karin Zimmer; Unni C Nygaard; Matej Orešič; Mikael Knip; Tuulia Hyötyläinen

doi:10.1016/j.envint.2020.105935

Prenatal exposure to perfluoroalkyl substances modulates neonatal serum phospholipids, increasing risk of type 1 diabetes

Environ Int. 2020 Oct:143:105935. doi: 10.1016/j.envint.2020.105935. Epub 2020 Jul 4.

Authors

Aidan McGlinchey¹, Tim Sinioja², Santosh Lamichhane³, Partho Sen³, Johanna Bodin⁴, Heli Siljander⁵, Alex M Dickens³, Dawei Geng², Cecilia Carlsson², Daniel Duberg², Jorma Ilonen⁶, Suvi M Virtanen⁷, Hubert Dirven⁴, Hanne Friis Berntsen⁸, Karin Zimmer⁹, Unni C Nygaard⁴, Matej Orešič¹⁰, Mikael Knip¹¹, Tuulia Hyötyläinen¹²

Affiliations

¹ School of Medical Sciences, Örebro University, 702 81 Örebro, Sweden.
² School of Science and Technology, Örebro University, 702 81 Örebro, Sweden.
³ Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland.
⁴ Division of Infection Control and Environmental Health, Norwegian Institute of Public Health, 0456 Oslo, Norway.
⁵ Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland.
⁶ Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, 20014 Turku, Finland; Department of Clinical Microbiology, Turku University Hospital, 20014 Turku, Finland.
⁷ Public Health Promotion Unit, National Institute for Health and Welfare, 00271 Helsinki, Finland; Unit of Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland; Tampere University Hospital, Research, Development and Innovation Center, Tampere, Finland; Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland.
⁸ Norwegian University of Life Sciences, 0102 Oslo, Norway; National Institute of Occupational Health, 0363 Oslo, Norway.
⁹ Tampere University Hospital, Research, Development and Innovation Center, Tampere, Finland.
¹⁰ School of Medical Sciences, Örebro University, 702 81 Örebro, Sweden; Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland. Electronic address: matej.oresic@utu.fi.
¹¹ Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland; Unit of Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland; Tampere University Hospital, Research, Development and Innovation Center, Tampere, Finland; Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland. Electronic address: mikael.knip@helsinki.fi.
¹² School of Science and Technology, Örebro University, 702 81 Örebro, Sweden. Electronic address: tuulia.hyotylainen@oru.se.

PMID: 32634666
DOI: 10.1016/j.envint.2020.105935

Abstract

In the last decade, increasing incidence of type 1 diabetes (T1D) stabilized in Finland, a phenomenon that coincides with tighter regulation of perfluoroalkyl substances (PFAS). Here, we quantified PFAS to examine their effects, during pregnancy, on lipid and immune-related markers of T1D risk in children. In a mother-infant cohort (264 dyads), high PFAS exposure during pregnancy associated with decreased cord serum phospholipids and progression to T1D-associated islet autoantibodies in the offspring. This PFAS-lipid association appears exacerbated by increased human leukocyte antigen-conferred risk of T1D in infants. Exposure to a single PFAS compound or a mixture of organic pollutants in non-obese diabetic mice resulted in a lipid profile characterized by a similar decrease in phospholipids, a marked increase of lithocholic acid, and accelerated insulitis. Our findings suggest that PFAS exposure during pregnancy contributes to risk and pathogenesis of T1D in offspring.

Keywords: Bile acids; Lipidomics; Mass spectrometry; PFAS; Type 1 diabetes.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Diabetes Mellitus, Experimental*
Diabetes Mellitus, Type 1*
Environmental Pollutants* / toxicity
Female
Finland / epidemiology
Fluorocarbons* / toxicity
Phospholipids
Pregnancy
Prenatal Exposure Delayed Effects* / epidemiology

Substances

Environmental Pollutants
Fluorocarbons
Phospholipids