Epigenetic transgenerational inheritance of altered stress responses

Crews, David; Gillette, Ross; Scarpino, Samuel V.; Manikkam, Mohan; Savenkova, Marina I.; Skinner, Michael K.

doi:10.1073/pnas.1118514109

Cited by 290 publications

(219 citation statements)

References 44 publications

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“…This idea is the intellectual foundation of the search for heritable histone modifications, DNA methylation, etc., yet is rarely directly tested. Strikingly, and underscoring our concern, in a few cases where data have been presented, the idea of allelespecific memory is either not tested or is directly refuted (Anway et al 2005;Pembrey et al 2006;Greer et al 2011;Crews et al 2012;Stern et al 2012;Voutounou et al 2012;Buescher et al 2013;Padmanabhan et al 2013;Wan et al 2013;Gapp et al 2014).…”

Section: The Test(s)mentioning

confidence: 99%

What Do You Mean, “Epigenetic”?

2015

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Interest in the field of epigenetics has increased rapidly over the last decade, with the term becoming more identifiable in biomedical research, scientific fields outside of the molecular sciences, such as ecology and physiology, and even mainstream culture. It has become increasingly clear, however, that different investigators ascribe different definitions to the term. Some employ epigenetics to explain changes in gene expression, others use it to refer to transgenerational effects and/or inherited expression states. This disagreement on a clear definition has made communication difficult, synthesis of epigenetic research across fields nearly impossible, and has in many ways biased methodologies and interpretations. This article discusses the history behind the multitude of definitions that have been employed since the conception of epigenetics, analyzes the components of these definitions, and offers solutions for clarifying the field and mitigating the problems that have arisen due to these definitional ambiguities.

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Section: The Test(s)mentioning

confidence: 99%

What Do You Mean, “Epigenetic”?

2015

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“…It is well known that adverse environments can significantly alter the epigenome and such modifications have been associated with several psychiatric disorders (Gräff and Mansuy, 2009;Ptak and Petronis, 2010;Tsankova et al, 2007). Recent work has shown that these environmentally-mediated epigenetic changes can be inherited through the paternal line and this can potentially have consequences on the inheritance of psychiatric disorders (Crews et al, 2012;Gapp et al, 2014). This emphasizes the need to identify not only genetic factors, but also environmental influences on the epigenetic mechanisms that may contribute to this inheritance of predisposition to mental illness (Toth, 2014).…”

Section: Introductionmentioning

confidence: 99%

Paternal environmental enrichment transgenerationally alters affective behavioral and neuroendocrine phenotypes

Yeshurun

Short

Bredy

et al. 2017

Psychoneuroendocrinology

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1016/j.psyneuen.2016.11.013 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractRecent studies have demonstrated that paternal stress in rodents can result in modification of offspring behavior. Environmental enrichment, which enhances cognitive stimulation and physical activity, modifies various behaviors and reduces stress responses in adult rodents. We investigated the transgenerational influence of paternal environmental enrichment on offspring behavior and physiological stress response. Adult C57BL/6J male mice (F0) were exposed to either environmental enrichment or standard housing for four weeks and then pair-mated with naïve females. The F2 generation was generated using F1 male offspring. Male and female F1 and F2 offspring were tested for anxiety using the elevated-plus maze and large open field at 8 weeks of age. Depression-related behavior was assessed using the forced-swim test. Hypothalamic-pituitary-adrenal (HPA) axis function was determined by quantification of serum corticosterone and adrenocorticotropic hormone (ACTH) levels at baseline and after forced-swim stress. Paternal environmental enrichment was associated with increased body weights of male F1 and F2 offspring. There was no significant effect on F1 offspring anxiety and depression-related behaviors. There were no changes in anxietyrelated behaviors in the F2 offspring, however these mice displayed a reduced latency to immobility in the forced-swim test. Furthermore, F2 females had significantly higher serum corticosterone levels post-stress, but not ACTH. These results show that paternal environmental enrichment exerts a sex-specific transgenerational impact on the behavioral and physiological response to stress. Our findings have implications for the modelling of psychiatric disorders in rodents.

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“…These altered expression patterns correlated with sex-specific altered anxiety-like behaviours up to the F3 generation [60]. The vinclozolin exposure three generations earlier even altered the murine response to chronic restraint stress [61].…”

Section: Epigenetics and Diseasementioning

confidence: 90%

Epigenetics and Transcriptomics to Detect Adverse Drug Effects in Model Systems of Human Development

Balmer

Leist

2014

Basic Clin Pharma Tox

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Prenatal exposure to environmental chemicals or drugs has been associated with functional or structural deficits and the development of diseases in later life. For example, developmental neurotoxicity (DNT) is triggered by lead, and this compound may predispose to neurodegenerative diseases in later life. The molecular memory for such late consequences of early exposure is not known, but epigenetic mechanisms (modification of the chromatin structure) could take this role. Examples and underlying mechanisms have been compiled here for the field of DNT. Moreover, we addressed the question as to what readout is suitable for addressing drug memory effects. We summarize how complex developmental processes can be modelled in vitro by using the differentiation of human stem cells. Although cellular models can never replicate the final human DNT phenotype, they can model the adverse effect that a chemical has on key biological processes essential for organ formation and function. Highly information-rich transcriptomics data may inform on these changes and form the bridge from in vitro models to human prediction. We compiled data showing that transcriptome analysis can indicate toxicity patterns of drugs. A crucial question to be answered in our systems is when and how transcriptome changes indicate adversity (as opposed to transient adaptive responses), and how drug-induced changes are perpetuated over time even after washout of the drug. We present evidence for the hypothesis that changes in the histone methylation pattern could represent the persistence detector of an early insult that is transformed to an adverse effect at later time-points in life.

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Epigenetic transgenerational inheritance of altered stress responses

Cited by 290 publications

References 44 publications

What Do You Mean, “Epigenetic”?

What Do You Mean, “Epigenetic”?

Paternal environmental enrichment transgenerationally alters affective behavioral and neuroendocrine phenotypes

Epigenetics and Transcriptomics to Detect Adverse Drug Effects in Model Systems of Human Development

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