New research from Helmholtz Munich and the German Centre for Diabetes Research sheds light on the potential health effects of overweight and diet-related dads on their offspring even before conception. The study’s conclusions may be used to create preventative health strategies for men who want to have children: the better the father’s diet, the less likely it is that their offspring will grow up to be obese or suffer from conditions like diabetes.
Head of Helmholtz Munich’s “Environmental Epigenetics” research group Dr. Raffaele Teperino and his colleagues have studied the effects of paternal nutrition on children’s health, in particular the preconceptional influence of food. The researchers concentrated on unique tiny RNA molecules found in sperm that are referred to be mitochondrial tRNA fragments (mt-tsRNAs; background information). Due to their ability to control gene expression, these RNAs are important in the transmission of health features.
The LIFE Child cohort, which comprises information from more than 3,000 families, provided the researchers with data for their investigation. The findings demonstrated that the father’s body weight had an impact on the children’s weight and susceptibility to metabolic disorders. This effect is independent of other variables like the mother’s weight, the genetic makeup of the parents, or the surroundings.
The study team then ran tests on mice to confirm the findings of their investigation. The mice were given a diet that was higher in fat than what would be found in a typical diet. This affected the animals’ reproductive systems, particularly the epididymis. In the male reproductive system, newly produced sperm develop in the epididymis.
Our study shows that sperm exposed to a high-fat diet in the mouse epididymis led to offspring with an increased tendency to metabolic diseases.
Raffaele Teperino
The study team carried out more laboratory investigations to delve deeper into the results. Through in-vitro fertilisation, or “fertilisation in a test tube,” they produced embryos. Teperino’s group discovered that mt-tsRNAs from sperm from mice exposed to a high-fat diet dramatically affected gene expression in early embryos. This in turn has an impact on the offspring’s growth and well-being.
Our hypothesis that acquired phenotypes over the course of life, such as diabetes and obesity, are transmitted via epigenetic mechanisms across generations, is reinforced by this study. Here, epigenetics serves as a molecular link between the environment and the genome, even across generational boundaries. This occurs not only through the maternal line but, as our research results indicate, also through the paternal line.
Prof. Martin Hrabě de Angelis
The results of the study by Helmholtz Munich researchers highlight the importance of paternal health prior to conception and present fresh ideas for preventive healthcare.
Our results suggest that preventive health care for men wishing to become fathers should receive more attention and that programs should be developed for this purpose, especially with regard to diet,
This can reduce the risk of diseases like obesity and diabetes in children.
Raffaele Teperino
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It’s common to refer to mitochondria as the cell’s power plants. They are separate entities from the DNA found in the nucleus of the cell. Usually passed from mothers to their kids, this mitochondrial DNA (mt-DNA) uses the intermediate mt-RNA to generate proteins in the mitochondria. It was previously believed that dads had little influence over the mitochondrial genetic composition of their children. But as new research, such as this one, demonstrates, sperm fertilise eggs by introducing mt-RNA fragments, or “mt-tsRNA.” The mt-tsRNAs regulate gene expression in the early embryo and are involved in epigenetics. By altering the activity of specific genes in the mitochondria, they might indirectly affect the development and health of the progeny. Fathers therefore have a significant, if indirect, impact on their children’s mitochondrial genetic imprinting and subsequent energy metabolism.
Source: Helmholtz Munich News
Journal Reference: Tomar, A., et al. “Epigenetic Inheritance of Diet-induced and Sperm-borne Mitochondrial RNAs.” Nature, 2024, pp. 1-8, https://doi.org/10.1038/s41586-024-07472-3.
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