Germline epigenetic inheritance: Challenges and opportunities for linking human paternal experience with offspring biology and health

Abstract

Recently, novel experimental approaches and molecular techniques have demonstrated that a male's experiences can be transmitted through his germline via epigenetic processes. These findings suggest that paternal exposures influence phenotypic variation in unexposed progeny–a proposal that runs counter to canonical ideas about inheritance developed during the 20th century. Nevertheless, support for paternal germline epigenetic inheritance (GEI) in nonhuman mammals continues to grow and the mechanisms underlying this phenomenon are becoming clearer. To what extent do similar processes operate in humans, and if so, what are their implications for understanding human phenotypic variation, health, and evolution? Here, we review evidence for GEI in human and nonhuman mammals and evaluate these findings in relation to historical conceptions of heredity. Drawing on epidemiological data, reproductive biology, and molecular embryology, we outline developments and opportunities for the study of GEI in human populations, emphasizing the challenges that researchers in this area still face.

Paternal adverse childhood experiences: Associations with infant DNA methylation

“…Human studies testing the effects of paternal exposures on epigenetic marks in offspring is complicated by numerous confounding factors, but a few studies suggest paternal experiences may associate with DNAm profiles of genes implicated in fetal development and connect to DNAm in adult offspring, likely through indirect mechanisms (Feinberg et al., 2015; Gettler et al., 2020; Knudsen et al., 2019; Milekic et al., 2015; Murphy et al., 2019; Potabattula et al., 2019; Rodgers et al., 2013; Ryan & Kuzawa, 2020; Soubry, 2018a, 2018b ; Soubry et al., 2016; Vansant, 2016). As the epigenomes of adult offspring have been shaped by experiences across the lifespan, possibly including paternal behavior and exposures, conclusions from these studies on the inheritance of a traumatic experience's biological memory from fathers are highly limited.…”

The evolutionary significance of human brown adipose tissue: Integrating the timescales of adaptation

“…Context-dependent epigenetic inheritance, also known as intergenerational epigenetic inheritance, is when the developing fetus or infant receives biological signals that convey information about either the current environment or the parent's lived experience. 98 The parental cues alter the offspring's epigenetic patterns and developing phenotype. This type of epigenetic inheritance is considered context-dependent because the induced phenotype is not passed on to the next generation independently of the direct exposure to the parent's biological signal.…”

Obesity, the Obesity Epidemic, and Metabolic Dysfunction: The Conundrum Presented by the Disconnect between Evolution and Modern Societies

“…Furthermore, while obese children/adolescents and adults both appear to respond to fibre diet interventions similarly (discussed in [34,35]), it is also likely that becoming obese during maturation and onset of puberty may impart unique aspects to obesity compared to adults, but details in this regard are still unclear [5]. While some obesity-risk may be inherited via epigenetic mechanisms from either parent (discussed in [15,36]), whether unique epigenetic mechanisms arise with childhood obesity prior to puberty or skeletal and physiological maturity, whether there are sex-specific epigenetic changes occurring, and whether the epigenetic changes occurring as a consequence of childhood obesity differ from those arising during adult obesity, largely remain the subject of current research.…”

“…As mentioned above, it is reported that there are >100 genetic risk factors for obesity (discussed in [10,13]). In addition, it is likely that epigenetic factors can also figure into multigenerational risk for obesity and related conditions (discussed in [14,15]), as well as other factors (discussed in [16]). The presence of such a large number of genetic and epigenetic risk factors for obesity has led some health care providers, and likely some patients to "throw up their hands in frustration" and attempt to deal with the issues in other ways (discussed in more detail below).…”