PMID- 35792514 OWN - NLM STAT- Publisher LR - 20231013 IS - 1873-6750 (Electronic) IS - 0160-4120 (Linking) VI - 166 DP - 2022 Aug TI - Exposure to a human relevant mixture of persistent organic pollutants or to perfluorooctane sulfonic acid alone dysregulates the developing cerebellum of chicken embryo. PG - 107379 LID - S0160-4120(22)00306-3 [pii] LID - 10.1016/j.envint.2022.107379 [doi] AB - 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. CI - Copyright (c) 2022. Published by Elsevier Ltd. FAU - Yadav, Ajay AU - Yadav A AD - Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 As, 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. FAU - Verhaegen, Steven AU - Verhaegen S AD - Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 As, Norway. Electronic address: steven.verhaegen@nmbu.no. FAU - Filis, Panagiotis AU - Filis P AD - Institute of Medical Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. Electronic address: pfilis@abdn.ac.uk. FAU - Domanska, Diana AU - Domanska D AD - 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. FAU - Lyle, Robert AU - Lyle R AD - 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. FAU - Sundaram, Arvind Y M AU - Sundaram AYM AD - Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway. Electronic address: arvind.sundaram@medisin.uio.no. FAU - Leithaug, Magnus AU - Leithaug M AD - Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway. Electronic address: magnus.leithaug@vetinst.no. FAU - Ostby, Gunn Charlotte AU - Ostby GC AD - Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 As, Norway. Electronic address: gunn.ostby@nmbu.no. FAU - Aleksandersen, Mona AU - Aleksandersen M AD - Department of Preclinical Sciences and Pathology, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 As, Norway. Electronic address: mona.aleksandersen@nmbu.no. FAU - Berntsen, Hanne Friis AU - Berntsen HF AD - Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 As, Norway; National Institute of Occupational Health, P.O. Box 5330 Majorstuen, NO-0304, Oslo, Norway. Electronic address: Hanne.Berntsen@stami.no. FAU - Zimmer, Karin Elisabeth AU - Zimmer KE AD - Department of Preclinical Sciences and Pathology, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 As, Norway. Electronic address: karin.zimmer@nmbu.no. FAU - Fowler, Paul A AU - Fowler PA AD - 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. FAU - Paulsen, Ragnhild Elisabeth AU - Paulsen RE AD - 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. FAU - Ropstad, Erik AU - Ropstad E AD - Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 As, Norway. Electronic address: erik.ropstad@nmbu.no. LA - eng PT - Journal Article DEP - 20220627 PL - Netherlands TA - Environ Int JT - Environment international JID - 7807270 SB - IM OTO - NOTNLM OT - Chicken embryo OT - Environmental toxicants OT - Neurodevelopment OT - Prenatal exposure OT - Proteomics OT - RNA-seq transcriptomics EDAT- 2022/07/07 06:00 MHDA- 2022/07/07 06:00 CRDT- 2022/07/06 10:00 PHST- 2022/02/03 00:00 [received] PHST- 2022/05/07 00:00 [revised] PHST- 2022/06/24 00:00 [accepted] PHST- 2022/07/07 06:00 [pubmed] PHST- 2022/07/07 06:00 [medline] PHST- 2022/07/06 10:00 [entrez] AID - S0160-4120(22)00306-3 [pii] AID - 10.1016/j.envint.2022.107379 [doi] PST - ppublish SO - Environ Int. 2022 Aug;166:107379. doi: 10.1016/j.envint.2022.107379. Epub 2022 Jun 27.