The study suggests that the father’s diet before conception affects the health of the children

Dr. Raffaele Teperino, head of the research group “Environmental Epigenetics” at Helmholtz Munich, together with his research team, has examined the influence of the father’s diet on the health of the children – in particular, the influence of the diet before conception. The researchers focused on special small RNA molecules in sperm, known as mitochondrial tRNA fragments (mt-tsRNAs). These RNAs play a key role in the inheritance of health traits by regulating gene expression.

For their study, the researchers used data from the LIFE Child cohort, which includes information from over 3,000 families. The analyzes showed that the body weight of the father affects the weight of the children and their susceptibility to metabolic diseases. This influence exists independently of other factors such as maternal weight, parental genetics or environmental conditions.

The paper was published in the journal Nature.

The father’s diet affects the children

To verify the results of their analysis, the research team then conducted experiments with mice. These mice were fed a high-fat diet, meaning food with a higher fat content than a normal diet. This had effects on the animal’s reproductive organs, including the epididymis. The epididymis is the area in the male reproductive system where newly formed spermatozoa mature.

“Our study shows that sperm exposed to a high-fat diet in the epididymis of mice led to offspring with an increased tendency to metabolic disease,” says Teperino.

To deepen the findings, the research team conducted additional studies in the laboratory. They created embryos through in-vitro fertilization (fertilization “in a test tube”). When Teperino’s team used sperm from mice that had been exposed to a high-fat diet, they found mt-tsRNA from these sperm in early embryos, significantly influencing gene expression. This, in turn, affects the development and health of the offspring.

“Our hypothesis that phenotypes acquired during life, such as diabetes and obesity, are transmitted through epigenetic mechanisms across generations is strengthened by this study.

“Here, epigenetics serves as a molecular link between the environment and the genome, even beyond the boundaries of generations. This happens not only through the maternal line, but, as the results of our research show, also through the paternal line,” explains Prof. Martin Hrabě de. Angelis, co-author of this study and Research Director at Helmholtz Munich.

Preventive health care for men who want to become fathers

The findings from researchers at Helmholtz Munich highlight the role of the father’s health before conception – and offer new approaches to preventive health care.

“Our results suggest that preventive health care for men who wish to become fathers should be given more attention and that programs should be developed for this purpose, especially regarding diet,” says Teperino. “This can reduce the risk of diseases such as obesity and diabetes in children.”

Indirect influence of fathers

Mitochondria have their own DNA, independent of the DNA in the cell’s nucleus. This mitochondrial DNA (mt-DNA) produces proteins in mitochondria via the intermediate mt-RNA and is usually inherited from mother to offspring.

Previously, it was assumed that fathers had no role in the genetic makeup of their offspring’s mitochondria. However, recent studies like this one now show that sperm carry fragments of mt-RNA (“mt-tsRNA”) to the egg during fertilization.

Mt-tsRNAs play a role in epigenetics, regulating gene expression in the early embryo: they can indirectly affect the development and health of offspring by modifying the activity of certain genes in the mitochondria. Thus, fathers have a significant, albeit indirect, influence on the genetic imprinting of mitochondria and thus on the energy metabolism of their children.