Richard Denison, Ph.D., is a Senior Scientist.
We’ve blogged here before about the growing evidence that environmental exposures can cause changes in gene expression – not to be confused with mutations, which are changes in the DNA itself. We’ve noted that these changes in how and when our genes are turned on and off may actually be heritable, along with any biological or behavioral changes they induce. That is, not only might the individual who is directly exposed suffer effects, but – and here’s the kicker – so might descendants who never experienced the original exposure.
Now, several new studies add even more evidence that epigenetic changes may be transgenerational. In the past 10 days, the Washington Post has run articles detailing three new studies in mice, each of which strongly indicate that dietary deficiencies and environmental exposures can reprogram DNA in ways that can be passed along to reside in the DNA of the offspring of the affected individuals.
The first article in the Post cited studies published in 2012 and earlier this year that found that exposure of female mice during pregnancy even to low doses of the endocrine disruptor, bisphenol A (BPA), induces changes in gene expression and biochemistry in the brain, resulting in changes in social behavior that persist for at least four generations.
The second article described a just-published study in which male mice were taught to associate the odor of – of all things – cherry blossoms with fear of a mild electric shock. When these mice were subsequently bred, their offspring – and their offspring’s offspring – continued to react to the aroma with symptoms of fear. The transmittance of this fear behavior was directly associated with the passing-down of changes in the epigenetic marks on genes that code for olfactory proteins. Moreover, the researchers showed that the changes were passed to the offspring via the fathers’ sperm.
The third article featured another new study in male mice that were fed a nutritionally deficient diet. The researchers studied the sperm of these mice and identified numerous abnormalities in epigenetic marks on genes associated with normal development, as well as with certain cancers and neurological and behavioral disorders. When these mice were bred, their offspring showed much higher rates of birth defects compared to the offspring of male mice fed a normal diet.
The latter two studies are particularly noteworthy in that they show that epigenetic marks can be paternally inherited. Conventional wisdom had been that only genetic mutations could be passed to offspring via sperm and that all epigenetic marks in fathers’ DNA were immediately “wiped clean” upon fertilization. Epigenetic marks in mothers’ DNA have also been thought to be erased, though more slowly. (A more nuanced and elaborate picture has emerged from more recent research, with some “imprinted” genes from both the mother and the father retaining their epigenetic marks during this critical period; see here and here.)
The agents at issue in these new studies differ dramatically: an endocrine-disrupting chemical, a specific odor, and dietary deficiencies. So do the transmitted traits: changes in social behavior, fear response, and birth defects. What is remarkable is that the same basic biological mechanism appears to be at play in each case: a change in the environment induces specific changes in gene expression mediated by alterations in epigenetic marks on the DNA; and those changes are stable enough to be passed along from one generation to the next, where they continue to dramatically alter the behavior or health of descendants who never experienced the original environmental change or exposure.
I don’t know about you, but this emerging science leaves me with a renewed sense of humility and the need for more caution before we unwittingly alter our environment in ways that may have adverse effects – literally on generations to come.