CE34 - Contaminants, écosystèmes et santé

Nuclear receptor signaling and endocrine disruption in a mollusk: the power of functional experiments – MusMod4EDC

Submission summary

Pervasive endocrine disrupting chemical (EDC) pollution is both a healthcare challenge and a threat to biodiversity. The impact of EDC pollution on humans, and other vertebrates, has been extensively studied, and numerous pathologies triggered by EDC exposure at different stages of life have been discovered. In contrast, apart from insects, very little is known about invertebrate endocrine systems, and virtually nothing is known about the toxicity of EDCs in invertebrates. Given that EDCs are found in plastics, personal care products and industrial commodities, vast amounts are released into the ocean by river outlets and wastewater influx, making EDC pollution also a growing problem for marine environments. Amongst invertebrates, mollusks are particularly sensitive to EDC exposure, which induces hermaphroditism in both gastropods and bivalves and causes phenotypes respectively referred to as imposex and intersex. The impact of EDCs is being addressed in ecotoxicology studies, which are generally based on either physiological or biochemical assays, but not on in vivo functional experiments, which has so far prevented the identification of the molecular modes of action of EDCs in marine invertebrates. There are, thus, currently massive gaps of knowledge in our understanding of EDC toxicology in marine invertebrates.
Nuclear receptors (NRs) are ligand-activated transcription factors crucial for regulating the vertebrate endocrine system, and their deregulation, by the binding of EDCs, is one of the leading causes of endocrine disruption in vertebrates. Given the importance of NR signaling in the vertebrate endocrine system, several standardized test systems used to detect endocrine disruption are based on measuring vertebrate NR activity. However, in invertebrates, virtually nothing is known about NR function and the roles of NR-dependent signaling in EDC toxicity. What has been shown is that the presence of a vertebrate NR homolog in an invertebrate is not automatically synonymous with the presence of a vertebrate-like signaling system downstream of this invertebrate NR. We are, thus, currently lacking even a basic understanding of the roles of NRs in endocrine disruption of invertebrates.
This project will remedy this shortcoming, as it will establish the planktonic embryos of the mussel M. galloprovincialis as a laboratory model system for studying NR functions and the roles they play in the toxicity of EDCs. More specifically, we propose to test the hypothesis that NR signaling mediates EDC-induced effects during development of the mussel M. galloprovincialis.
The project is divided into four tasks that will (1) yield detailed information on the expression of NRs during mussel development, both spatiotemporally and quantitatively, (2) compile a detailed characterization of EDC effects on mussel embryos and a list of molecular markers for EDC responses in mussels, (3) determine how genes affected by EDC treatments are regulated by NRs and (4) establish the roles played by NRs during mussel development as well as their contribution to endocrine disruption in mussels. Altogether, by creating novel techniques and resources for M. galloprovincialis, our proposed work will be the first to define NR functions and activities during mussel development and to demonstrate, in vivo, how EDCs modify these functions and activities, hence establishing the planktonic embryos of M. galloprovincialis as a potent study system bridging developmental biology and functional ecotoxicology. The molecular markers for EDC responses that we will identify in the course of this project, for example, will be extremely useful for marine monitoring programs and ecotoxicological surveys to detect endocrine disruption. Given that mussels are a sentinel species used around the world to survey marine environments, international monitoring programs, such as Mussel Watch, will thus benefit greatly from this project.

Project coordination

Remi Dumollard (Laboratoire de Biologie du développement de Villefranche-sur-Mer)

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.

Partner

EDEC Endocrine Disruptors and Emergent Contaminants
LBDV Laboratoire de Biologie du développement de Villefranche-sur-Mer
LBDV Laboratoire de Biologie du développement de Villefranche-sur-Mer

Help of the ANR 533,176 euros
Beginning and duration of the scientific project: January 2022 - 48 Months

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