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, 55 92-101. doi:10.1016/j.neuro.2016.05.011

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ404241_OA.pdf Full text (open access) application/pdf 288.18KB 0

Author Ponsonby, Anne-Louise
Symeonides, Christos
Vuillermin, Peter
Mueller, Jochen
Sly, Peter D.
Saffery, Richard
Title Epigenetic regulation of neurodevelopmental genes in response to in utero exposure to phthalate plastic chemicals: how can we delineate causal effects?
Formatted title
Epigenetic regulation of neurodevelopmental genes in response to in utero exposure to phthalate plastic chemicals: how can we delineate causal effects?
Journal name NeuroToxicology   Check publisher's open access policy
ISSN 1872-9711
0161-813X
Publication date 2016-07-01
Year available 2016
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/j.neuro.2016.05.011
Open Access Status File (Author Post-print)
Volume 55
Start page 92
End page 101
Total pages 10
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Language eng
Subject 2800 Neuroscience
3005 Toxicology
Abstract 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.
Formatted abstract
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.
Keyword Bisphenol A
Causal evidence
Developmental origins
DNA methylation
Early birth cohort
Fetal programming
Intrauterine environment
Neonatal epigenome
Observational epidemiology
Phthalate
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: HERDC Pre-Audit
Child Health Research Centre Publications
National Research Centre for Environmental Toxicology Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 3 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 5 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 11 Sep 2016, 10:32:25 EST by System User on behalf of Learning and Research Services (UQ Library)