Epigenetic regulation of neurodevelopmental genes in response to in utero exposure to phthalate plastic chemicals: how can we delineate causal effects?

Ponsonby, Anne-Louise, Symeonides, Christos, Vuillermin, Peter, Mueller, Jochen, Sly, Peter D. and Saffery, Richard 2016, Epigenetic regulation of neurodevelopmental genes in response to in utero exposure to phthalate plastic chemicals: how can we delineate causal effects?, Neurotoxicology, vol. 55, pp. 92-101, doi: 10.1016/j.neuro.2016.05.011.

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Title Epigenetic regulation of neurodevelopmental genes in response to in utero exposure to phthalate plastic chemicals: how can we delineate causal effects?
Author(s) Ponsonby, Anne-Louise
Symeonides, Christos
Vuillermin, PeterORCID iD for Vuillermin, Peter orcid.org/0000-0002-6580-0346
Mueller, Jochen
Sly, Peter D.
Saffery, Richard
Journal name Neurotoxicology
Volume number 55
Start page 92
End page 101
Total pages 10
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2016-07
ISSN 0161-813X
1872-9711
Keyword(s) phthalate
bisphenol A
developmental origins
DNA methylation
neonatal epigenome
fetal programming
intrauterine environment
early birth cohort
causal evidence
observational epidemiology
Summary Accumulating evidence, from animal models and human observational studies, implicates the in utero (and early postnatal) environment in the 'programming' of risk for a variety of adverse outcomes and health trajectories. The modern environment is replete with man-made compounds such as plastic product chemicals (PPC), including phenols and phthalates. Evidence from several human cohorts implicates exposure to these chemicals in adverse offspring neurodevelopment, though a direct causal relationship has not been firmly established. In this review we consider a potential causal pathway that encompasses epigenetic human variation, and how we might test this mechanistic hypothesis in human studies. In the first part of this report we outline how PPCs induce epigenetic change, focusing on the brain derived neurotrophic factor (BDNF) gene, a key regulator of neurodevelopment. Further, we discuss the role of the epigenetics of BDNF and other genes in neurodevelopment and the emerging human evidence of an association between phthalate exposure and adverse offspring neurodevelopment. We discuss aspects of epidemiological and molecular study design and analysis that could be employed to strengthen the level of human evidence to infer causality. We undertake this using an exemplar recent research example: maternal prenatal smoking, linked to methylation change at the aryl hydrocarbon receptor repressor (AHRR) gene at birth, now shown to mediate some of the effects of maternal smoking on birth weight. Characterizing the relationship between the modern environment and the human molecular pathways underpinning its impact on early development is paramount to understanding the public health significance of modern day chemical exposures.
Language eng
DOI 10.1016/j.neuro.2016.05.011
Field of Research 119999 Medical and Health Sciences not elsewhere classified
1109 Neurosciences
1115 Pharmacology And Pharmaceutical Sciences
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Elsevier
Persistent URL http://hdl.handle.net/10536/DRO/DU:30085325

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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