Exposure to a human relevant mixture of persistent organic pollutants or to perfluorooctane sulfonic acid alone dysregulates the developing cerebellum of chicken embryo
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...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-08-01
|
| Series: | Environment International |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412022003063 |
| _version_ | 1818006044423487488 |
|---|---|
| author | Ajay Yadav Steven Verhaegen Panagiotis Filis Diana Domanska Robert Lyle Arvind Y.M. Sundaram Magnus Leithaug Gunn Charlotte Østby Mona Aleksandersen Hanne Friis Berntsen Karin Elisabeth Zimmer Paul A. Fowler Ragnhild Elisabeth Paulsen Erik Ropstad |
| author_facet | Ajay Yadav Steven Verhaegen Panagiotis Filis Diana Domanska Robert Lyle Arvind Y.M. Sundaram Magnus Leithaug Gunn Charlotte Østby Mona Aleksandersen Hanne Friis Berntsen Karin Elisabeth Zimmer Paul A. Fowler Ragnhild Elisabeth Paulsen Erik Ropstad |
| author_sort | Ajay Yadav |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T04:55:11Z |
| format | Article |
| id | doaj.art-970f14a02db340179e709415cbd9492b |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-04-14T04:55:11Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-970f14a02db340179e709415cbd9492b2022-12-22T02:11:10ZengElsevierEnvironment International0160-41202022-08-01166107379Exposure to a human relevant mixture of persistent organic pollutants or to perfluorooctane sulfonic acid alone dysregulates the developing cerebellum of chicken embryoAjay Yadav0Steven Verhaegen1Panagiotis Filis2Diana Domanska3Robert Lyle4Arvind Y.M. Sundaram5Magnus Leithaug6Gunn Charlotte Østby7Mona Aleksandersen8Hanne Friis Berntsen9Karin Elisabeth Zimmer10Paul A. Fowler11Ragnhild Elisabeth Paulsen12Erik Ropstad13Department 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; Corresponding author.Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 Ås, NorwayInstitute of Medical Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UKInstitute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Pathology, Oslo University Hospital-Rikshospitalet, Oslo, NorwayDepartment of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway; Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, NorwayDepartment of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, NorwayDepartment of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, NorwayDepartment of Production Animal Clinical Sciences, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 Ås, NorwayDepartment of Preclinical Sciences and Pathology, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 Ås, NorwayDepartment 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, NorwayDepartment of Preclinical Sciences and Pathology, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 Ås, NorwayInstitute of Medical Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UKSection for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, NO-0316 Oslo, NorwayDepartment of Production Animal Clinical Sciences, Norwegian University of Life Sciences, P.O. Box 5003, NO-1432 Ås, NorwayPrenatal 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.http://www.sciencedirect.com/science/article/pii/S0160412022003063Chicken embryoEnvironmental toxicantsNeurodevelopmentPrenatal exposureRNA-seq transcriptomicsProteomics |
| spellingShingle | Ajay Yadav Steven Verhaegen Panagiotis Filis Diana Domanska Robert Lyle Arvind Y.M. Sundaram Magnus Leithaug Gunn Charlotte Østby Mona Aleksandersen Hanne Friis Berntsen Karin Elisabeth Zimmer Paul A. Fowler Ragnhild Elisabeth Paulsen Erik Ropstad Exposure to a human relevant mixture of persistent organic pollutants or to perfluorooctane sulfonic acid alone dysregulates the developing cerebellum of chicken embryo Environment International Chicken embryo Environmental toxicants Neurodevelopment Prenatal exposure RNA-seq transcriptomics Proteomics |
| title | Exposure to a human relevant mixture of persistent organic pollutants or to perfluorooctane sulfonic acid alone dysregulates the developing cerebellum of chicken embryo |
| title_full | Exposure to a human relevant mixture of persistent organic pollutants or to perfluorooctane sulfonic acid alone dysregulates the developing cerebellum of chicken embryo |
| title_fullStr | Exposure to a human relevant mixture of persistent organic pollutants or to perfluorooctane sulfonic acid alone dysregulates the developing cerebellum of chicken embryo |
| title_full_unstemmed | Exposure to a human relevant mixture of persistent organic pollutants or to perfluorooctane sulfonic acid alone dysregulates the developing cerebellum of chicken embryo |
| title_short | Exposure to a human relevant mixture of persistent organic pollutants or to perfluorooctane sulfonic acid alone dysregulates the developing cerebellum of chicken embryo |
| title_sort | exposure to a human relevant mixture of persistent organic pollutants or to perfluorooctane sulfonic acid alone dysregulates the developing cerebellum of chicken embryo |
| topic | Chicken embryo Environmental toxicants Neurodevelopment Prenatal exposure RNA-seq transcriptomics Proteomics |
| url | http://www.sciencedirect.com/science/article/pii/S0160412022003063 |
| work_keys_str_mv | AT ajayyadav exposuretoahumanrelevantmixtureofpersistentorganicpollutantsortoperfluorooctanesulfonicacidalonedysregulatesthedevelopingcerebellumofchickenembryo AT stevenverhaegen exposuretoahumanrelevantmixtureofpersistentorganicpollutantsortoperfluorooctanesulfonicacidalonedysregulatesthedevelopingcerebellumofchickenembryo AT panagiotisfilis exposuretoahumanrelevantmixtureofpersistentorganicpollutantsortoperfluorooctanesulfonicacidalonedysregulatesthedevelopingcerebellumofchickenembryo AT dianadomanska exposuretoahumanrelevantmixtureofpersistentorganicpollutantsortoperfluorooctanesulfonicacidalonedysregulatesthedevelopingcerebellumofchickenembryo AT robertlyle exposuretoahumanrelevantmixtureofpersistentorganicpollutantsortoperfluorooctanesulfonicacidalonedysregulatesthedevelopingcerebellumofchickenembryo AT arvindymsundaram exposuretoahumanrelevantmixtureofpersistentorganicpollutantsortoperfluorooctanesulfonicacidalonedysregulatesthedevelopingcerebellumofchickenembryo AT magnusleithaug exposuretoahumanrelevantmixtureofpersistentorganicpollutantsortoperfluorooctanesulfonicacidalonedysregulatesthedevelopingcerebellumofchickenembryo AT gunncharlotteøstby exposuretoahumanrelevantmixtureofpersistentorganicpollutantsortoperfluorooctanesulfonicacidalonedysregulatesthedevelopingcerebellumofchickenembryo AT monaaleksandersen exposuretoahumanrelevantmixtureofpersistentorganicpollutantsortoperfluorooctanesulfonicacidalonedysregulatesthedevelopingcerebellumofchickenembryo AT hannefriisberntsen exposuretoahumanrelevantmixtureofpersistentorganicpollutantsortoperfluorooctanesulfonicacidalonedysregulatesthedevelopingcerebellumofchickenembryo AT karinelisabethzimmer exposuretoahumanrelevantmixtureofpersistentorganicpollutantsortoperfluorooctanesulfonicacidalonedysregulatesthedevelopingcerebellumofchickenembryo AT paulafowler exposuretoahumanrelevantmixtureofpersistentorganicpollutantsortoperfluorooctanesulfonicacidalonedysregulatesthedevelopingcerebellumofchickenembryo AT ragnhildelisabethpaulsen exposuretoahumanrelevantmixtureofpersistentorganicpollutantsortoperfluorooctanesulfonicacidalonedysregulatesthedevelopingcerebellumofchickenembryo AT erikropstad exposuretoahumanrelevantmixtureofpersistentorganicpollutantsortoperfluorooctanesulfonicacidalonedysregulatesthedevelopingcerebellumofchickenembryo |