Exposure to a human relevant mixture of persistent organic pollutants or to perfluorooctane sulfonic acid alone dysregulates the developing cerebellum of chicken embryo.

Autor: Yadav A; Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 Ås, Norway; Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, NO-0316 Oslo, Norway. Electronic address: ajay.yadav@nmbu.no., Verhaegen S; Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 Ås, Norway. Electronic address: steven.verhaegen@nmbu.no., Filis P; Institute of Medical Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. Electronic address: pfilis@abdn.ac.uk., Domanska D; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Pathology, Oslo University Hospital-Rikshospitalet, Oslo, Norway. Electronic address: diana.domanska@medisin.uio.no., Lyle R; Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway; Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway. Electronic address: robert.lyle@medisin.uio.no., Sundaram AYM; Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway. Electronic address: arvind.sundaram@medisin.uio.no., Leithaug M; Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway. Electronic address: magnus.leithaug@vetinst.no., Østby GC; Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 Ås, Norway. Electronic address: gunn.ostby@nmbu.no., Aleksandersen M; Department of Preclinical Sciences and Pathology, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 Ås, Norway. Electronic address: mona.aleksandersen@nmbu.no., Berntsen HF; Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 Ås, Norway; National Institute of Occupational Health, P.O. Box 5330 Majorstuen, NO-0304, Oslo, Norway. Electronic address: Hanne.Berntsen@stami.no., Zimmer KE; Department of Preclinical Sciences and Pathology, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 Ås, Norway. Electronic address: karin.zimmer@nmbu.no., Fowler PA; Institute of Medical Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. Electronic address: p.a.fowler@abdn.ac.uk., Paulsen RE; Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, NO-0316 Oslo, Norway. Electronic address: r.e.h.paulsen@farmasi.uio.no., Ropstad E; Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 Ås, Norway. Electronic address: erik.ropstad@nmbu.no.
Jazyk: angličtina
Zdroj: Environment international [Environ Int] 2022 Aug; Vol. 166, pp. 107379. Date of Electronic Publication: 2022 Jun 27.
DOI: 10.1016/j.envint.2022.107379
Abstrakt: Prenatal exposure to persistent organic pollutants (POPs) is associated with neurodevelopmental disorders. In the present study, we explored whether a human-relevant POP mixture affects the development of chicken embryo cerebellum. We used a defined mixture of 29 POPs, with chemical composition and concentrations based on blood levels in the Scandinavian population. We also evaluated exposure to a prominent compound in the mixture, perfluorooctane sulfonic acid (PFOS), alone. Embryos (n = 7-9 per exposure group) were exposed by injection directly into the allantois at embryonic day 13 (E13). Cerebella were isolated at E17 and subjected to morphological, RNA-seq and shot-gun proteomics analyses. There was a reduction in thickness of the molecular layer of cerebellar cortex in both exposure scenarios. Exposure to the POP mixture significantly affected expression of 65 of 13,800 transcripts, and 43 of 2,568 proteins, when compared to solvent control. PFOS alone affected expression of 80 of 13,859 transcripts, and 69 of 2,555 proteins. Twenty-five genes and 15 proteins were common for both exposure groups. These findings point to alterations in molecular events linked to retinoid X receptor (RXR) signalling, neuronal cell proliferation and migration, cellular stress responses including unfolded protein response, lipid metabolism, and myelination. Exposure to the POP mixture increased methionine oxidation, whereas PFOS decreased oxidation. Several of the altered genes and proteins are involved in a wide variety of neurological disorders. We conclude that POP exposure can interfere with fundamental aspects of neurodevelopment, altering molecular pathways that are associated with adverse neurocognitive and behavioural outcomes.
(Copyright © 2022. Published by Elsevier Ltd.)
Databáze: MEDLINE
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