Fathers Leave Their Marks
Evidence of paternal epigenetic inheritance is rare but intriguing.
Posted Jan 29, 2014
Epigenetic inheritance represents a way to transmit molecular modifications to genes to subsequent generations. Some alteration, like in methylation or chromatin packing, of genes in a father’s sperm may be transmitted to his children. The gene itself is no different, but how it is expressed is. How large is this potential stamp of fatherhood upon children’s lives?
When David Crews and colleagues treated male rats with vinclozolin, which has antiandrogen properties, the males showed alterations in the methylation patterns of their genes. More dramatically, those effects were manifest three generations later, with great-grandson pups having lower mating success. This example is enough to make one shake in his epigenetic boots. It’s not the only experimental demonstration of such effects in rodents either. Amanda Drake and colleagues found that rat fathers who had been treated with dexamethasone, a synthetic glucocorticoid, had offspring with lower birth weight and altered liver activity. Imagine this for a moment: a rat father has only provided his sperm (not his surname or money for college) but that has had non-genetic impacts on characteristics in his offspring.
One of the central questions to paternal epigenetic inheritance is the mechanism by which these effects are passed from fathers to offspring. In many plant examples, epigenetic marks are passed directly from parent to offspring plant, but this is far rarer in mammals like rats or humans. Indeed, the epigenetic marks in a man’s sperm tend to be erased, which allows the genes in his sperm an epigenetic blank slate that is then written on with social and nutritional cues during his offspring’s development. This also suggests that most human similarities in the epigenetic marks of fathers and offspring are likely due to shared environments (i.e., similarities in the environment of fathers and offspring may induce similar epigenetic marks in both generations). If epigenetic marks are retained during sperm formation and fertilization, that is a more exciting and novel prospect to many scholars—a new mode of Lamarckian inheritance from father to offspring.
Have scientists underestimated the scope of human paternal epigenetic inheritance? As shown in a recent review by Adelheid Soubry and colleagues, a variety of studies indicate that men exposed to occupational hazards or toxins (by perhaps working in a paint factory or through exposure to Agent Orange during Vietnam) have offspring with a higher incidence of medical conditions, including various forms of cancer. It has largely been assumed that those associations trace to genetic mutations or DNA damage passed in a man’s sperm to his progeny. But scholars note that epigenetic inheritance could instead be consistent with those same patterns. The long-recognized existence of genomic imprinting in humans and other mammals (see Christopher Badcock’s Psychology Today blog: http://www.psychologytoday.com/blog/the-imprinted-brain) demonstrates that epigenetic marks are sometimes transmitted from father to offspring, influencing offspring traits. The experimental work on nonhuman models (like those rats above) further demonstrates the plausibility of human paternal epigenetic inheritance. Ultimately, molecular studies are required to determine whether epigenetic marks underlie traits passed from fathers to offspring.
In the attempt to discern how men leave a distinct paternal imprint, this body of work invites us to think outside of the typical genetic or socioeconomic boxes. As of now, evidence of human paternal epigenetic inheritance is rare, but provocative.
Crews, D., et al. (2007). Transgenerational epigenetic imprints on mate preference. Proceedings of the National Academy of Sciences, 104, 5942-5946.
Drake, A. J., and Liu, L. (2010). Intergenerational transmission of programmed effects: public health consequences. Trends in Ecology and Evolution, 21, 206-213.
Soudbry, A., Hoyo, C., Jirtle, R. L., and Murphy, S. K. (2014). A paternal environmental legacy: evidence for epigenetic inheritance through the male germ line. Bioessays, in press.