How Can Dietary Choices Influence Intergenerational Inheritance?

In many animal species, the mother's diet and the environment in which she lives affect the health of her future offspring, as well as subsequent generations. To a large extent, this is done through the so-called epigenetic inheritance. Environmental factors do not change the nucleic acid sequence in parents' cells, but they can modify the level of gene expression, for example by changing their methylation. As the latest research results say, information on the mother's state of health and nutrition can also be passed onto offspring directly - through fats, proteins and various metabolites. Scientists are still conducting research related to the impact of nutrients in food consumed by mothers on the development of the nervous system in future generations.

The proper functioning of the nervous system depends on the uninterrupted transmission of the signal between neurons. Microtubules forming the cell cytoskeleton are responsible for “smooth” information flow. In the species Caenorhabditis elegans, belonging to nematodes, there are neurons that provide information on the touch and coordinate the response to this type of stimulus. These cells are located in the posterolateral part of the animal’s body and undergo gradual degradation with age, and very intensively when animals are deprived of the mec17 gene – this leads to destabilization of microtubules and thus to axonal transport deterioration. These neurons also become much more sensitive to damage in animals with an excessively elongated body, which is in turn caused by the mutation in the lon-2 gene.

Australian scientists have assumed that one of the food ingredients that can protect nerve cells from damage is ursolic acid. It‘s a compound of natural origin found, among others, in apples. The aim of the researchers was to establish a mechanism by which ursolic acid may act as a neuroprotectant and whether its administration to mothers may affect the nervous system of their offspring.

The scientists conducted experiments on the nematodes of the Caenorhabditis elegans species. They used two genetically modified strains: one with a mutation in the mec-17 gene and the other in the lon-2 gene. The control group were wild-type animals. Researchers exposed nematodes from the F0 generation (parents) at various stages of development to ursolic acid. They then checked whether the use of the test compound affected the incidence of “breaks” within neurons in three consecutive generations of nematodes. To establish the mechanism of action of this compound, researchers conducted a number of molecular biology analyzes, including next generation sequencing. After verification of how the parents’ metabolism changes after administration of ursolic acid, they determined key molecules whose expression is regulated by this acid. They tracked their expression and transport in the bodies of nematodes. They also ran experiments based on the direct transport of metabolites to oocytes and checked the sensitivity of neurons to damage in offspring born from those stimulated reproductive cells.

It turned out that exposing the F0 generation to ursolic acid during oocyte production significantly increased neuron resistance to damage in two successive generations of nematodes. Ursolic acid caused this effect by increasing the production of a bioactive particle belonging to the group of sphingolipids – sphingosine-1-phosphate (SP1). Interestingly, scientists have found that ursolic acid stimulates the production of SP1 in the nematode intestines, from where it is then transported to oocytes. The results of an additional in vitro experiment confirmed that the transport of the SP1 molecule to oocytes of mothers from the F0 generation reduced the sensitivity of axons to damage in their offspring. SP1 is therefore a key molecule through which intergenerational protection of the nervous system occurs. 

The authors of the work have been able to show that the mother’s diet can affect the health of future generations, and this is due to specific molecules that are fat metabolites. Perhaps in the long run the discovery of researchers from Australia will encourage future mothers to consume more products that are rich in ursolic acid.  However, further research is needed to confirm the similar impact of this compound on people.