A dad’s diet affects his sperm — and his sons’ health

A dad’s sperm records his diet — and this record affects his sons’ metabolism, according to a study of mice and humans1.

Giving male mice a high-fat diet raises levels of some types of RNA in their sperm, the study found. The research also showed that the male offspring of male mice on this unhealthy diet had metabolic problems such as glucose intolerance, a characteristic of diabetes. The sons of human dads with a high body mass index (BMI) exhibited similar problems, according to epidemiological analysis.

The study was published in Nature on 6 June.

Written in sperm
Studies have shown that mothers can pass on metabolic traits to their offspring. As for fathers, Qi Chen, a reproductive-biology researcher at the University of Utah School of Medicine in Salt Lake City, and his team showed in 2016 that fertilized mouse eggs injected with sperm RNA from dads on a high-fat diet developed into mice with metabolic disorders2. Research shows that the ripple effects of a parent’s diet are caused by changes not to the offspring’s genome but to their ‘epigenome’ — the collection of chemical tags hanging from DNA and its associated proteins.

For the Nature study, male mice ate a high-fat diet for two weeks. The study’s authors found that this regimen led to changes in a type of RNA in the sperm’s mitochondria — the structures inside cells that generate energy. The affected molecules, called transfer RNAs, are intermediate products in the process of transcribing DNA into proteins.

In particular, sperm of mice that ate fatty food had more short fragments of transfer RNA than did the sperm of mice on a low-fat diet. Such RNA fragments can act as epigenetic regulators of the genome — for example, turning up or down the activity of certain mitochondrial genes.

Stressed mitochondria
The results make sense: a high-fat diet stresses mitochondria, says Raffaele Teperino, lead author of the study and an environmental-epigenetics researcher at Helmholtz Center Munich in Neuherberg, Germany. When stressed, mitochondria make more RNA to produce more energy.

The mitochondria’s response is a trade-off, says Chen, who was not involved in the study. The increase in mitochondrial activity gives the sperm enough oomph to swim to reach the egg, but the extra mitochondrial RNAs are also passed down from father to embryo, changing the information that the embryo gets from its father and damaging its health.

Teperino’s team looked not only at cells but also at the health of humans whose dads were overweight and mice whose dads ate fatty food. Of the latter group, about 30% had metabolic disorders, the researchers found. Further experiments showed that these mouse offspring had much more mitochondrial tRNA from their dads than did sons of mouse dads on the low-fat diet. The authors also analysed data from 3,431 human children and found that higher paternal BMI at conception was linked to worse offspring metabolic health.

Fragmentary evidence
A technical limitation of the study is that the sequencing method used for some of the experiments detects only whole RNA molecules. Because of this, the study couldn’t show whether the fragmented RNA was transferred from father to embryo. “We assume that fragments are also transferred, but we can’t prove it,” says Teperino.

The fact that the mouse dads in the study passed on only metabolic problems to male offspring — which is consistent with his own 2016 paper — particularly intrigues Chen. “This suggests that the X sperm and the Y sperm are carrying different information,” he says. Why X and Y sperm would do that is “a very good question for future studies”, he says.

Chen says the study means that, if you make sperm, “you should eat healthy. It will affect the information carried in your sperm. It will affect your offspring”.

doi: https://doi.org/10.1038/d41586-024-01623-2