Environment + Genes = Us. Over the 20th century as our knowledge of biology increased, this simple equation seemed to be the general overriding theory as to what ultimately controls the development of our bodies, brains, and lifespan. This complex, and often mysterious, interaction between our DNA blueprint and environmental exposure determined what illnesses we developed, how long we lived, and even our psychological well being.

More recently, the science of epigenetics has begun to explain exactly how our gene activity can be modulated by external environmental factors. A variety of epigenetic mechanisms have been uncovered, revealing how factors like stress or diet can alter the expression of certain genes. Understanding how these epigenetic triggers function promises to fundamentally expand our ability to tinker with biological systems. Instead of directly altering a DNA sequence to make a small change, we can now work to simply silence, or reduce, the expression of a single gene causing an unwanted effect.

But a great debate has been raging for some time questioning just how heritable these epigenetic cues are. When a mother and father's DNA join to create a new life, is this just a mix of their DNA blueprints, or are epigenetic cues also transferred from generation to generation?

In 2015, a study was published claiming that the children of Holocaust survivors were more likely to develop depression, anxiety and other psychological disorders. The implication was that trauma could be transmitted across generations via epigenetic alterations.

Unsurprisingly, the study was controversial, with one researcher dubbing it, "the over-interpreted epigenetics study of the week," and suggesting, "the story is typical of many in the field of epigenetics, with conclusions drawn based on uninterpretable studies."

While it is generally agreed that epigenetic cues can be transferred to a child by a mother during pregnancy, there are still major questions surrounding the idea that experiences earlier in a parent's life could cause fundamental changes that can be passed down to subsequent generations.

A fascinating new study led by researchers at the German Center for Neurodegenerative Diseases (DZNE) has revealed that in mice models, epigenetically modulated microRNAs in a father's sperm can indeed be passed down to offspring. This compelling study provides clear evidence that some kinds of epigenetic markers can be passed on to a new generation.

To evaluate how epigenetic inheritance could work a group of mice were subjected to what is called environmental enrichment through a combination of physical exercise and cognitive training known to enhance synaptic plasticity in animal models. The researchers then examined the offspring of those mice and found they also displayed the same cognitive improvements generated by their parents. Compared to a control group's offspring, this new generation displayed improved synaptic plasticity, particularly in the hippocampus.

Homing in on the mechanism behind this epigenetic transfer the team examined the paternal sperm and identified several microRNA molecules that could explain the inherited characteristics. Two molecules, miRNA212 and miRNA132, in particular, were found in increased levels in the paternal sperm of the mice that experienced environmental enrichment. These specific molecules are known to influence gene activity related to the formation of synapses in the brain.

Further experiments extracted those specific microRNA molecules from the sperm and injected them into fertilized egg cells. The mice that were subsequently born displayed enhanced learning ability and increased synaptic plasticity.

"For the first time, our work specifically links an epigenetic phenomenon to certain microRNAs", says Andre Fischer, one of the scientists working on the project.

It's still early days in the research and many questions do remain, most prominently that of whether this same phenomenon occurs in humans. The next stage in the work will be to examine human sperm to find out whether miRNA212 and miRNA132 accumulate in response to a person's physical or mental activity. This would help clarify whether these epigenetic RNA cues are transferred to sperm after acute environmental experiences.

Another epigenetic mechanism being studied for heritability is called DNA methylation. This process involves methyl groups interacting with a DNA molecule to alter the expression of a gene, and in some cases silence it entirely. Many cancers, for example, are known to occur through a process of hyper-methylation silencing tumor suppressor genes and causing the cancer to progress.

Research has shown that epigenetic DNA methylation marks are mostly erased in primordial gene cells, the precursors to eggs and sperm. This acts as a kind of reset button for each new generation, stopping too many negative environmental factors from influencing a person's offspring.

However, a 2013 study from Cambridge scientists found that some methylation markers can bypass this erasure process and be passed onto subsequent generations. This, again, is research still at a very early stage, but it explains many fascinating historical accounts of trans-generational health effects being inherited from parents or even grandparents that had suffered through times of famine.

"It seems that while the precursors to sperm and eggs are very effective in erasing most methylation marks, they are fallible and at a low frequency may allow some epigenetic information to be transmitted to subsequent generations," says Jamie Hackett, lead on the Cambridge research. "The inheritance of differential epigenetic information could potentially contribute to altered traits or disease susceptibility in offspring and future descendants."

It is still decidedly unclear how significant the process of epigenetic inheritance in humans actually is in determining the characteristics of a new generation, but the implications of this new research area could be profoundly significant.

The new DZNE research was published in the journal Cell Reports.

Source: DZNE