Immune stimulation can help increase aquaculture production by altering epigenetic modifications

Scientists at the Institut de Ciències del Mar of the CSIC have demonstrated that some stimulations of the immune system during the early stages of fish development can trigger epigenetic modifications that lead to changes in the sexual phenotype. This could have important implications for aquaculture production in those species where the female has the greatest growth, since the more females there are, the higher the production.

Zebrafish is used as a model species in scientific research / ICM-CSICEpigenetics studies how the environment and history of the individual influence the expression of genes and the phenotype, and more precisely, the transmission of acquired characters from one generation to another. In fishes, the sexual phenotype, that is, the sex (ovary or testicle) of an individual, depends on both the genotype and the environmental factors in which they live.

Now, a study by the Institut de Ciències del Mar (ICM-CSIC) published recently in the journal Developmental & Comparative Immunology has shown that, in the case of fish, immune system stimulation can trigger epigenetic modifications, in particular, modifications of the sexual phenotype, which could have important implications for aquaculture production.

These modifications refer to variations in the levels of DNA methylation, a biological process by which methyl groups are added to the DNA molecule. DNA methylation is usuallty associated with the silencing of gene expression. There are indications that methylation changes are located in regions that appear to be sex-independent in order to protect the genome of cells from possible attack by bacteria.

To carry out the study, the authors immuno-stimulated, during the process of sexual differentiation, a group of zebrafish (Danio rerio) -a model species in scientific research- with the wall of a bacterium (Aeromonas hydrophila) which is commonly found on aquaculture farms and can be used to boost the immune response in some fish vaccines.

Thus, they realized that three hours after immuno-stimulation, there were modifications in the levels of DNA methylation in genes in the innate response of fish, that is, the first response of the immune system that leads to inflammation, but not yet the synthesis of antibodies.

The entry of the bacterial wall occurred through the gills and was recruited to the pronephros, an embryonic organ of the larvae that gives rise to the anterior kidney and is known as the quintessential immune organ of fish. According to the researchers, when the walls of the bacterium reach the pronephros, its process of degradation by macrophages and other cells of the immune system responsible for the innate activation response begins.

"This study has allowed us to show that an immuno-stimulation during the sexual differentiation of zebrafish is, on the one hand, responsible for changing the levels of DNA methylation, and on the other, able to increase the number of females," states Laia Ribas, an ICM-CSIC researcher and the leading author of the study. In this sense, the expert adds that "this could have important applications in aquaculture, as it could increase production and help to better understand the alterations of methylation and its consequences on the sexual phenotype."

Another major finding of the study is that changes in sexual phenotype depend on concentration, bacterial strain, and time and frequency of exposure to immuno-stimulating molecules, as, for example, it has been shown that very low or very high wall doses of Aeromonas hydrophila have failed to increase the number of females. In addition, no modifications in the sexual phenotype were observed in short exposures.

In face of future research, the researchers plan to focus on other species of fish of commercial interest, such as European bass (Dicentrarchus labrax). "The idea is to see not only sex changes, but also whether the epigenetic modifications given in the early stages of development that can affect, among other things, the reproductive quality of adults," concludes Ribas.

Reference article
Moraleda-Prados, J., Caballero-Huertas, M., Valdivieso, A., Joly, S., Ji, J., Roher, N., & Ribas, L. (2020). Epigenetic differences in the innate response after immune stimulation during zebrafish sex differentiation. Developmental & Comparative Immunology, 103848.

Elena Martínez Batalla (ICM-CSIC)