The Sins Of The Fathers: How What Your Father Ate Could Determine Who You Are

Scientists at the Institute of Molecular Biology in Mainz, Germany, have made a breakthrough discovery proving that what a father eats or experiences can affect his offspring through molecules called RNAs, which are packaged into "granules" in his sperm. These RNAs can affect his children's health, for better or worse.

Humans live in a constantly changing environment and face numerous challenges, including food shortages, changes in diet, diseases, and extreme temperatures. To survive, the body changes how it processes food and energy - for example, by storing more energy as fat. But could our environment cause changes not only in ourselves but also in any future children we have?

Scientists know of several cases where changes in an individual's diet before they had children later affected their children's health or even grandchildren. But how does the offspring's body 'know' what sort of diet their parents had? One possibility is that a parent's diet causes changes to molecules in their eggs or sperm. Such molecules include small RNAs, which modify how a cell 'reads' the instructions in its DNA. Changes to RNAs in the sperm or eggs could inform the offspring's body about their parents' diet, allowing it to make changes that help it survive better on the same diet.

Several examples of RNAs passing from parents to offspring have been found in worms and mice. However, many of these studies focused on the mother, as egg cells are much larger than sperm and have more space to store small RNAs. Sperm cells even remove most of their internal contents to swim faster. So how could RNAs be passed from fathers to offspring?

Prof. Ketting and his team have discovered that RNAs are passed to offspring through "granules" in the father's sperm. Granules are condensed bubbles of liquid, jelly, or solids inside cells that act like storage boxes for molecules. In their study, Prof. Ketting and his team looked at the sperm cells of C. elegans, a small transparent worm. They discovered a new type of granule in the worm's sperm, which they named PEI (Paternal Epigenetic Inheritance) granules. "PEI granules can be seen as a particular treasure chest within sperm cells, in which important objects can be secured for the next generation," explains Prof. Ketting.

When Dr. Schreier, the project's lead scientist, removed components necessary for PEI granule activity, no small RNAs were passed on to the worm's offspring. This was the first time scientists have discovered how fathers pass small RNAs to their offspring. "It was simply amazing to literally see before my eyes how small RNAs are inherited through sperm. I am sure that mechanisms similar to what we discovered will also be found in other animals, including humans".

Such RNAs from our parents may allow our bodies to better adjust to the diet our parents ate. Conversely, making bad dietary choices, such as smoking or an unhealthy diet, might alter sperm RNAs and harm our children's health for generations to come. It may also be that sperm RNAs change as fathers age. In effect, this discovery shows that who we are is determined not only by the DNA we receive from our parents but also by a wealth of additional information from the environment they experienced.

Further details

Further information can be found at www.nature.com/articles/s41556-021-00827-2

René Ketting is Executive and Scientific Director at the Institute of Molecular Biology. Further information about research in the Ketting lab can be found at www.imb.de/ketting