The sins of the fathers: how what your father ate could determine who you are

PRESS RELEASE

8 January – 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 makes many changes in the way 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 the health of their children 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 animals such as 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 so they can swim faster. So how could RNAs be passed from fathers to offspring?

Now, 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 very specific treasure chest within sperm cells, in which important objects can be secured for the next generation”, explains Prof. Ketting.

When Dr Schreier, the lead scientist of the project, 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 actually 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}

^{Cheryl Li is a Science Writer at the Institute of Molecular Biology (IMB).}

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

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

^{About the Institute of Molecular Biology gGmbH}

^{The Institute of Molecular Biology gGmbH (IMB) is a centre of excellence in the life sciences that was established in 2011 on the campus of Johannes Gutenberg University Mainz (JGU). Research at IMB focuses on the cutting-edge fields of epigenetics, genome stability, ageing and RNA biology. The institute is a prime example of successful collaboration between a private foundation and government: The Boehringer Ingelheim Foundation has committed 154 million euros to be disbursed from 2009 until 2027 to cover the operating costs of research at IMB. The State of Rhineland-Palatinate has provided approximately 50 million euros for the construction of a state-of-the-art building and is giving a further 52 million in core funding from 2020 until 2027. For more information about IMB, please visit: www.imb.de}

^{Boehringer Ingelheim Foundation}

^{The Boehringer Ingelheim Foundation is an independent, non-profit organization that is committed to the promotion of the medical, biological, chemical, and pharmaceutical sciences. It was established in 1977 by Hubertus Liebrecht (1931–1991), a member of the shareholder family of the Boehringer Ingelheim company. Through its Perspectives Programme Plus 3 and its Exploration Grants, the Foundation supports independent junior group leaders. It also endows the international Heinrich Wieland Prize, as well as awards for up-and-coming scientists in Germany. In addition, the Foundation funds institutional projects in Germany, such as the Institute of Molecular Biology (IMB), the department of life sciences at the University of Mainz, and the European Molecular Biology Laboratory (EMBL) in Heidelberg. www.bistiftung.de}

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^{Institute of Molecular Biology gGmbH (IMB), Ackermannweg 4, 55128 Mainz, Germany}

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