Gonçalves Athanasio, Camila , Sommer, Ulf, Viant, Mark R., Chipman, James Kevin and Mirbahai, Leda (2018) Use of 5-azacytidine in a proof-of-concept study to evaluate the impact of pre-natal and post-natal exposures, as well as within generation persistent DNA methylation changes in Daphnia. Ecotoxicology, 27 (5). pp. 556-568. doi:10.1007/s10646-018-1927-3 ISSN 0147-6513.

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Abstract

Short-term exposures at critical stages of development can lead to delayed adverse effects long after the initial stressor has been removed, a concept referred to as developmental origin of adult disease. This indicates that organisms’ phenotypes may epigenetically reflect their past exposure history as well as reflecting chemicals currently present in their environment. This concept has significant implications for environmental monitoring. However, there is as yet little or no implementation of epigenetics in environmental risk assessment. In a proof-of-principle study we exposed Daphnia magna to 5-azacytidine, a known DNA de-methylating agent. Exposures covered combinations of prenatal and postnatal exposures as well as different exposure durations and recovery stages. Growth, the transcription of genes and levels of metabolites involved in regulating DNA methylation, and methylation levels of several genes were measured. Our data shows that prenatal exposures caused significant changes in the methylome of target genes, indicating that prenatal stages of Daphnia are also susceptible to same level of change as post-natal stages of Daphnia. While the combination of pre- and postnatal exposures caused the most extreme reduction in DNA methylation compared to the control group. Furthermore, some of the changes in the methylation patterns were persistent even after the initial stressor was removed. Our results suggest that epigenetic biomarkers have the potential to be used as indicators of past chemical exposure history of organisms and provide strong support for implementing changes to the current regimes for chemical risk assessment to mimic realistic environmental scenarios.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH426 Genetics
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Epigenetics, Daphnia, Methylation
Journal or Publication Title:	Ecotoxicology
Publisher:	Springer
ISSN:	0147-6513
Official Date:	July 2018
Dates:	Date Event July 2018 Published 5 April 2018 Available 14 March 2018 Accepted
Volume:	27
Number:	5
Page Range:	pp. 556-568
DOI:	10.1007/s10646-018-1927-3
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	4 February 2019
Date of first compliant Open Access:	4 February 2019
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID CAPES/BEX8572-12-7 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior http://dx.doi.org/10.13039/501100002322 NBAF863 [NERC] Natural Environment Research Council http://dx.doi.org/10.13039/501100000270 UNSPECIFIED university of birmingham UNSPECIFIED

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