Prospective Intergenerational Consequences of Paternal Stress Experiences on Offspring Immune Health

A close relationship between immune regulation and neuropsychiatric disorders is becoming more apparent. Studies have now uncovered key mechanisms for stress to manifest as physiological maladaptations. Stress is a persistent issue with broad-ranging implications for the mental and physical health of society, including its broad impact on immune health. Evidence shows that stress activates pro-inflammatory cytokine pathways that contribute to the long-term dysregulation of the hypothalamus-pituitary-adrenal axis. Within the past decade, preclinical discoveries have demonstrated multigenerational impacts of stress transmitted via the male germ line. While similar epigenetic processes exist in humans, the occurrence of intergenerational epigenetic inheritance in humans remains highly controversial. However, there is mounting evidence that a parental history of stress can be a risk factor for developing anxiety and depressive traits, leading to a more recent hypothesis that the parental history of exposures to stress also influences offspring immune function via epigenetic inheritance. In this regard, greater progress has been made in understanding the maternal influence while little is known of the paternal contribution. In this review, we will discuss the potential for non-genetic environmental factors (e.g. stress exposures) to compromise the male germline epigenetic constitution (e.g. non-coding RNA content and extent of DNA methylation) resulting in a compromised immunological state of health of their offspring.