Father’s Pre-conception Diet Could Affect Long-term Health of His Future Offspring; How Do Mitochondrial Fragments in the Sperm Affect Genetic Makeup?

It is widely known that a mother's health is important before and during conception. But how about fathers? A new study reveals that paternal diet plays a surprisingly important role in the health of future children.

Indirect Influence of Fathers

Mitochondria are usually described as the powerhouse of the cell. This organelle has its own DNA, which is independent of the DNA in the cell nucleus. This mitochondrial DNA (mt-DNA) produces proteins in the mitochondria through the intermediate (mt-DNA) and is usually inherited from mothers to offspring.

It was previously thought that fathers do not play a role in the genetic makeup of their children's mitochondria. However, it was also discovered that the sperm cells contain special small RNA molecules called mitochondrial tRNA fragments (mt-tsRNAs).

This means that fathers may have an important, indirect influence on the genetic imprinting of mitochondria. It can also be assumed that they affect the energy metabolism of their offspring.

Influence of Paternal Diet

At Helmholtz Munich, a team of researchers has examined the effect of a father's diet on children's health, particularly on the influence of diet before conception. The results of their study are discussed in the paper "Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs."

Led by Dr. Raffaele Teperino, the team focused on mitochondrial tRNA fragments. These RNA molecules are known for their important role in the inheritance of health traits through the regulation of gene expression.

In this study, the experts used data from LIFE Child, a large population-based longitudinal childhood cohort study conducted in Leipzig City, Germany. This cohort includes data from more than 3,000 families.

The analyses showed that the body weight of fathers affects the health of the children as well as their vulnerability to metabolic diseases. Such influence independently exists from other factors like parental genetics, the mother's weight, and environmental conditions.

To confirm this result, Teperino and colleagues decided to conduct experiments with mice. These animals were fed a high-fat diet, which means that they consumed food with a higher fat content than a normal diet.

The high-fat diet was shown to have effects on the reproductive organs of the mice, including the epididymis, where freshly formed sperm cells mature. The study reveals that sperm exposed to a high-fat diet in the epididymis results in offspring with an increased tendency to metabolic diseases.

Additional studies were conducted by the research team to deepen the findings. The research team used sperm from mice with a high-fat diet to create embryos through in-vitro fertilization. It was found that mt-tsRNAs from these sperm influenced gene expression, affecting the development and health of the offspring.

According to research co-author Professor Martin Hrabě de Angelis, the study reinforced their hypothesis that acquired phenotypes over the course of one's life can be transmitted through epigenetic mechanisms across generations. This occurs not only through the maternal line but also through the paternal line.

The result of this study does not only underline the role of paternal health before pregnancy, but it also suggests preventive health care for men who plan to become fathers in the future.

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