Review articlePrenatal stress and epigenetics
Introduction
A growing body of evidence from human and animal studies has demonstrated that adversity in early life, especially in the critical developmental window of intrauterine life, has programming effects on health outcomes in postnatal life. The literature has also documented that prenatal stress can adversely impact on offspring outcomes throughout childhood that persist into adulthood (Beydoun and Saftlas, 2008, Eriksson, 2010). Epigenetics could be one process driving the association between prenatal stress and fetal programming. In the current review we summarize the recent findings from both animal and human research, demonstrating the associations between prenatal stress and DNA methylation change, DNA methylation and offspring health outcomes and the potential mediation effect of DNA methylation on exposure-phenotype associations. Evidence reported here from research on genes whose DNA methylation levels were associated with prenatal stress has shed light on how epigenetic mechanism could mediate biological processes involved in stress regulation.
Section snippets
Fetal programming and the developmental origins of health and disease (DOHaD)
The fetal programming hypothesis (Barker 1990), often referred to as the Developmental Origins of Health and Disease (DOHaD) theory (Gluckman et al., 2010), has been applied to both animals (Kapoor et al., 2008, McArdle et al., 2006, Schneider and Moore, 2000, Son et al., 2007, Weinstock, 2001, Welberg and Seckl, 2001) and human research (Barker, 1995, Barker and Martyn, 1997, Egliston et al., 2007, O'Connor et al., 2002, O'Connor et al., 2003, Oken and Gillman, 2003). Programming refers to
Prenatal stress
Research on prenatal maternal stress suggests that maternal exposure to a severe stressor modifies a wide range of somatic systems in the fetus, and may increase risk for a variety of disorders in adulthood (Charil et al., 2010, DiPietro, 2004, Glover, 2011, Huizink et al., 2004, Weinstock, 2008). But what is “stress”? The model by Lazarus and Folkman (Lazarus and Folkman, 1984) suggests that an individual is first confronted with an external event: the objective stressor. An individual must
Epigenetics: an overview
The Greek prefix “epi” means “on top of” or “over”. The term “epigenetics” refers to a series of chemical modifications to chromatin that regulate genomic transcription. Epigenetic modifications could be stable and passed on to future generations, but they could also be dynamic and change in response to environmental stimuli. The three major epigenetic mechanisms include DNA methylation (covalent modification of cytosine with a methyl group), histone modification (acetylation, methylation,
Discussion and perspectives
The prenatal period is a vulnerable time for fetal development both in animals and humans. Although considerable discoveries in this field have been made, many challenges still need to be addressed.
Conclusions
Based on the DOHaD theory, in utero exposure to environmental stress in both animals and humans could result in long-term epigenome alterations and which further lead to consequences for adaptation and development in the unborn offspring and, potentially, in the offspring. In this review, we outlined evidence from animal and human prenatal research supporting the view that prenatal stress could lead to lasting, broad and functionally organized signatures in DNA methylation which, in turn, could
Acknowledgement
This research was supported by grants from the Canadian Institute of Health Research (CIHR) (MOP-1150067), the Natural Sciences and Engineering Research Council of Canada Discovery (#05519) and the EU BRAINAGE (Project 279281).
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