Transgenerational actions of pollutant in fish: implications of Epigenetics in ecotoxicology – TRACE
Epigenetics is the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail a change in DNA code. One of the most studied epigenetic mechanisms is DNA methylation. DNA methylation, which refers to the addition of a methyl group to the cytosine base, is involved in fundamental biological functions such as development and cell differentiation. In recent years, the role of epigenetics in the etiology of human diseases has received increasing attention. There is increasing evidence that environmental factors such as nutrition, maternal care, temperature or pollutants can strongly affect the epigenetic status of mammalian cells. These defects or unintended changes in DNA methylation marks can be associated with negative health outcomes such as embryonic lethality, tumor genesis, diabetes, infertility and even, in some cases, to transgenerational diseases. Despite such evidences, epigenetics research is surprisingly very limited in ecotoxicology. Nowadays, most of the current knowledge relating to the effects of pollutants on epigenetic marks comes from rodent models and experimental investigations during which exposure to contaminants was carried out during embryogenesis. Such data are currently lacking for non-mammalian species and for long-term exposure which are environmentally more relevant. Integrating researches across the fields of epigenetics and ecotoxicology could lead to a better understanding of the long-lasting impacts of contaminants on organisms and populations.
In this context, the present proposal aims to test whether (i) low-dose and life-long exposure to a nonessential trace metal, cadmium (Cd), can induce changes in the methylome of fish (Danio rerio) and (ii) metal-induced epigenetic modifications can be transmitted to the unexposed offspring. We propose to work at two life stages, at the larval and adult stages (on both males and females). Indeed, genome-wide pattern of DNA methylation do not persist throughout life but undergoes precise and coordinated changes at defined stage of development. It thus appears interesting to investigate a potential effect of Cd on the DNA methylation status of cells throughout animal life. Although this is still largely unexplored, if a pollutant impairs the DNA reprogramming events that occur during animal life or induce errors in DNA methylation marks, this could not only impair organism development but also impact the population by affecting the reproductive capacities of animals. By taking advantage of next generation sequencing, the methylome of larvae and gonads, brain and liver of sexually differentiated control and metal-contaminated fish of the F0 and F1 (ie a generation that experienced Cd stress as germ line) generations will be determined. Transgenerational inheritance will be investigated on two subsequent generations that will be no longer exposed to metal by measuring the methylation level of a limited number of selected genes from the genome-wide analysis. In order to investigate the impacts associated at the organism and population levels, some more classical endpoints will be determined at each generation and at each stage of development. Thus, we propose to follow the hatching success and the mortality rate at the embryonic stage. At the larval stage, we propose to carry out behavioral and anatomopathological investigations. At the adult stage, the spawning success, sex ratio, fish growth and condition will be recorded. We will also test whether epigenetic modifications can alter the plasticity of fish.
The expected results of this project will bring new and original data about the potential implications of epigenetics in ecotoxicology and more precisely upon (i) chronic stress-induced epigenetic modifications and associated phenotypic changes, (ii) the persistence of transgenerational effects, (iii) epigenetically induced adaptation and/or chronic diseases face to low-dose and life-long chemical exposure.
Monsieur Fabien Pierron (Environnements et Paleoenvironnements Océaniques et Continentaux)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
EPOC Environnements et Paleoenvironnements Océaniques et Continentaux
Help of the ANR 279,828 euros
Beginning and duration of the scientific project: September 2016 - 36 Months