Biologists first observed “transgenerational epigenetic inheritance in plants. But, over the past few years, evidence has accumulated showing that the phenomenon also occurs in rodents and humans.

For example, in humans it has been shown that if a maternal diet is low in carbs, there is a higher probability that any progeny will be overweight later in life. Experiments have also shown that environment can affect DNA in germ cells and thus change the behavior of subsequent generations even before they undergo meiosis.

A study was published last year in Nature Neuroscience in which mice were conditioned to associate a specific scent with danger or discomfort. The paternal traumatic exposure was transferred to their F1 and F2 offspring, even when they had never been exposed to such a smell before. Finally, using in vitro fertilization and cross-fostering studies, it was found that behavior alterations were really inherited and not socially transmitted from the F0 generation.

Male mice were exposed to acetophenone (a chemical with sweet smell) and then shocked with mild foot shock five times a day for three consecutive days and were then mated with unexposed females. When their young grew up, many were more sensitive to acetophenone than to other odors. What is even more interesting is that this behavioral sensitivity was complemented by neuroanatomical modifications of the acetophenone receptors. How exactly does olfactory stimulation in the F0 generation become linked to sperm is an intriguing question for which Ressler and Dias, the researchers behind the aforementioned paper, can only speculate that it happens through methylation. Sequencing of bisulfite PCR amplicons in sperm from conditioned males and their offspring revealed epigenetic marks (CpG hypomethylation in the specific acetophenone receptor gene) that could be the basis for such inheritance.

According to new research some epigenetic changes acquired during a lifetime can be passed down from one generation to the next but the exact mechanism behind it is still not well understood. These results give us a new insight into understanding the increase in neuropsychiatric disorders, obesity, diabetes and metabolic disorders in recent years in which instances a multigenerational approach has, need to be considered.

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By Mojca Jez, PhD, Researcher at the Blood Transfusion Centre SI