Hormones and Behavior 59: 306-314 (2011)
Epigenetics and the origins of paternal effects

James P. Curley, Rahia Mashoodh, Frances A. Champagne
Department of Psychology, Columbia University, Schermerhorn Hall, 1190 Amsterdam Avenue, New York, NY 10027, USA

Abstract

Though there are multiple routes through which parents can influence their offspring, recent studies of environmentally induced epigenetic variation have highlighted the role of non-genomic pathways. In addition to the experience-dependent modification of DNA methylation that can be achieved via mother-infant interactions, there has been increasing interest in the epigenetic mechanisms through which paternal influences on offspring development can be achieved. Epidemiological and laboratory studies suggest that paternal nutritional and toxicological exposures as well as paternal age and phenotypic variation can lead to variations in offspring and, in some cases, grand-offspring development. These findings suggest a potential epigenetic germline inheritance of paternal effects. However, it may be important to consider the interplay between maternal and paternal influences as well as the experimental dissociation between experience-dependent and germline transmission when exploring the role of epigenetic variation within the germline as a mediator of these effects. In this review, we will explore these issues, with a particular focus on the potential role of paternally induced maternal investment, highlight the literature illustrating the transgenerational impact of paternal experiences, and discuss the evidence supporting the role of epigenetic mechanisms in maintaining paternal effects both within and across generations.


Interestingly, children of alcoholic fathers exhibit hyperactivity and reduced cognitive performance, but only if the alcoholic father is also their biological father, demonstrating the potential for these induced effects being preconceptual in nature (Hegedus et al., 1984; Tarter et al., 1984).


For example, when mated with males sporting red leg bands (i.e. artificially made more attractive), female zebra finches laid heavier eggs, had offspring that spent more time begging, and had faster growth rates than offspring of females who were paired randomly with males sporting green leg bands (i.e. artificially made unattractive) (Gilbert et al., 2006). In contrast, another study reported increased egg volumes and elevated yolk carotenoids and testosterone levels when female zebra finches were paired with less attractive males (Bolund et al., 2009). Likewise, young female mallards increased their egg volume when mated with highly attractive males (Cunningham and Russell, 2000), but older females increase their egg volume when mated with less attractive males (Bluhm and Gowaty, 2004). The decision to withhold resources or increase maternal investment may involve an interaction between mate quality and the reproductive life-history of the female, the availability of attractive males within a population, or the degree of reproductive skew (Harris and Uller, 2009). It has also been argued that reproductive compensation is more likely to occur in situations where females are not allowed to make a free choice with whom to mate (Gowaty et al., 2007; Harris and Uller, 2009; Sheldon, 2000).


In order for environmentally induced or stochastic changes in these epigenetic modifications to be faithfully transmitted to offspring they have to escape two major phases of DNA epigenetic reprogramming when the epigenome (i.e. genome-wide methylation patterns) are subjected to extensive demethylation and remethylation. The first wave occurs in the zygote, where the paternal genome is actively demethylated shortly after fertilization and then remethylated just prior to implantation of the blastocyst (Shi and Wu, 2009). The second wave occurs during embryogenesis with DNA demethylation occurring in the PGCs as they migrate down the genital ridge to the early bipotential gonad. Following sex determination, DNA remethylation occurs in germ cells in a sex-specific fashion (Allegrucci et al., 2005). Significantly, some classes of genes within the germline have the unique capacity to retain their altered methylation states across multiple generations despite these waves of epigenetic reprogramming during development. In particular, retrotransposable elements and imprinted genes appear to be both sensitive to environmental exposures and capable of retaining epigenetic marks (Lane et al., 2003).