PMID- 27208563
OWN - NLM
STAT- MEDLINE
DCOM- 20171117
LR  - 20180816
IS  - 1872-9711 (Electronic)
IS  - 0161-813X (Linking)
VI  - 55
DP  - 2016 Jul
TI  - Epigenetic regulation of neurodevelopmental genes in response to in utero 
      exposure to phthalate plastic chemicals: How can we delineate causal effects?
PG  - 92-101
LID - S0161-813X(16)30089-4 [pii]
LID - 10.1016/j.neuro.2016.05.011 [doi]
AB  - 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.
CI  - Copyright (c) 2016 Elsevier B.V. All rights reserved.
FAU - Ponsonby, Anne-Louise
AU  - Ponsonby AL
AD  - Murdoch Childrens Research Institute, Royal Children's Hospital, University of 
      Melbourne, Parkville, Victoria, Australia. Electronic address: 
      anne-louise.ponsonby@mcri.edu.au.
FAU - Symeonides, Christos
AU  - Symeonides C
AD  - Murdoch Childrens Research Institute, Royal Children's Hospital, University of 
      Melbourne, Parkville, Victoria, Australia.
FAU - Vuillermin, Peter
AU  - Vuillermin P
AD  - Murdoch Childrens Research Institute, Royal Children's Hospital, University of 
      Melbourne, Parkville, Victoria, Australia; Deakin University, Geelong, Victoria, 
      Australia; Child Health Research Unit, Barwon Health, Geelong, Victoria, 
      Australia.
FAU - Mueller, Jochen
AU  - Mueller J
AD  - National Research Centre for Environmental Toxicology, University of Queensland, 
      Brisbane, Australia.
FAU - Sly, Peter D
AU  - Sly PD
AD  - Child Health Research Centre, University of Queensland, Brisbane, Australia.
FAU - Saffery, Richard
AU  - Saffery R
AD  - Murdoch Childrens Research Institute, Royal Children's Hospital, University of 
      Melbourne, Parkville, Victoria, Australia.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20160518
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Phthalic Acids)
RN  - 6O7F7IX66E (phthalic acid)
RN  - 7171WSG8A2 (BDNF protein, human)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - DNA Methylation
MH  - Epigenesis, Genetic/*drug effects
MH  - Female
MH  - Humans
MH  - Male
MH  - Neurodevelopmental Disorders/*chemically induced/metabolism
MH  - Phthalic Acids/*toxicity
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*chemically induced/physiopathology
OTO - NOTNLM
OT  - Bisphenol A
OT  - Causal evidence
OT  - DNA methylation
OT  - Developmental origins
OT  - Early birth cohort
OT  - Fetal programming
OT  - Intrauterine environment
OT  - Neonatal epigenome
OT  - Observational epidemiology
OT  - Phthalate
EDAT- 2016/05/22 06:00
MHDA- 2017/11/29 06:00
CRDT- 2016/05/22 06:00
PHST- 2016/02/25 00:00 [received]
PHST- 2016/05/03 00:00 [revised]
PHST- 2016/05/17 00:00 [accepted]
PHST- 2016/05/22 06:00 [entrez]
PHST- 2016/05/22 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
AID - S0161-813X(16)30089-4 [pii]
AID - 10.1016/j.neuro.2016.05.011 [doi]
PST - ppublish
SO  - Neurotoxicology. 2016 Jul;55:92-101. doi: 10.1016/j.neuro.2016.05.011. Epub 2016 
      May 18.