Epigenetic Risk Factors for Diseases: A Transgenerational Perspective

Abstract

Each individual is determined by a combination of genetic and non-genetic factors that together shape physiological and biological functions during development and adulthood. While genetic features are embedded in the DNA sequence inherited from parents, non-genetic features (which include epigenetic modifi cations) are acquired through experiences and environmental exposure across life. However, it is now acknowledged that non-genetic features can also be inherited from parents and propagate across generations. This chapter discusses the concept of non-genetic germline inheritance in mammals and examines possible routes of transmission of non-genetic information involving germline-dependent and germline-independent modes of transfer. It reviews current evidence that environmental factors can induce non-genetic alterations in the germline that can impact behavioral and physiological features in the offspring. This chapter also addresses the underlying molecular mechanisms, provides initial insight into the implication of epigenetic marks and noncoding RNAs in male germ cells, and questions the way non-genetic modifi cations can be induced and maintained in germ cells. It highlights promising areas of current research and refl ects on evolutionary perspectives and future challenges.

Anhedonia Following Early-Life Adversity Involves Aberrant Interaction of Reward and Anxiety Circuits and Is Reversed by Partial Silencing of Amygdala Corticotropin-Releasing Hormone Gene

“…Stress influences the expression and function of several hormones and mediators, including glucocorticoids and their brain receptors and the neuropeptide corticotropin-releasing factor (CRF; encoded by the Crh gene). Early-life stress induces potent epigenetic mechanisms to persistently alter the expression of several of these molecules, and thus change enduringly responses to subsequent stress, as well as vulnerability and resilience to stress-related emotional disorders (24–29). A significant body of work has analyzed the effects of early-life stress on glucocorticoid receptors in regions influencing pleasure/reward function such as the hippocampus (26,27), amygdala (28,29) and prefrontal cortex (28,30,31).…”

Population history with invasive predators predicts innate immune function response to early life glucocorticoid exposure

“…predators, aggressive competitors, pathogens) is likely to lead to injury or increase infection risk (Cox and John-Alder, 2007;Ezenwa et al, 2012), it may be maladaptive to compromise immune function in response to stressors. Such transgenerational immune changes could be induced by epigenetic processes (Bohacek and Mansuy, 2016;Fitzpatrick and Wilson, 2003;Mostoslavsky and Bergman, 1997;Teitell and Richardson, 2003), and/or maternal effects (Hasselquist et al, 2012;Ismail et al, 2015; Veru et al, 2014) on the immune system directly or indirectly (e.g. effects on other systems that have cascading effects on the immune system).…”

Intricacies of aetiology in intrafamilial degenerative disease

“…During spermatogenesis, most histones are replaced by protamines that facilitate DNA compaction. The remaining histones and newly acquired protamines can undergo post-translational modification and regulate gene expression ( Bohacek and Mansuy, 2016 ). A study proposes that environmentally induced liver injury gives rise to a soluble factor in serum that modulates histone methylation of PPARγ chromatin in sperm and impacts the hepatic wound healing response in subsequent generations ( Zeybel et al , 2012 ).…”