Neuroendocrine disruption in marine shellfish: uncovering cellular and developmental mechanisms of action using a sentinel bioindicator species

A major component of anthropogenic change is the release of pollutants into the environment. Endocrine Disruptors (EDs) are important pollutants found in wastewater effluents that alter the normal functioning of the endocrine system. EDs released into the environment are of particular concern as the neuroendocrine system is responsible for regulating a complex array of whole organism physiologies such as: stress responses, development, metabolism, growth, immune responses.

EDs can have dramatic effects on physiology at very low concentrations (ng/L) and can have transgenerational consequences by effecting both the exposed individual and its offspring.

EDs found in the environment include polychlorinated biphenyls (PCBs), organochlorine pesticides, plasticizers, surfactants and pharmaceuticals. This project will focus on pharmaceutical EDs that are specifically designed to target the endocrine system of humans. They are widely prescribed drugs and have a direct route to aquatic and marine ecosystems via water treatment plants.

For example, in 2021, nine out of ten wastewater effluents tested in the UK and Europe contained an ED called dutasteride, commonly used to treat prostate cancer, at concentrations between 6-127 ng/L [1].

To date, most research has focussed on pharmaceutical ED exposure in vertebrates, as the effects often mirror the target human mode of action. It was initially thought that invertebrates would not be affected by pharmaceutical EDs as their endocrine systems are divergent and fundamentally different to vertebrates. Surprisingly, research is beginning to document that pharmaceutical EDs dramatically affect the neuroendocrine system of invertebrates [2].

Despite the importance of the neuroendocrine system in regulating whole organism physiology, it is not well characterised in invertebrates, especially molluscs. Yet, in terms of biomass, biodiversity, and functional trait diversity, molluscs are essential components of every aquatic ecosystem in the UK, as well as being important harvest and aquaculture industries in Scotland and Northern Ireland.

This project will study the mode of action of pharmaceutical EDs using an environmentally and ecologically sentinel species - the invasive slipper limpet Crepidula fornicata. This species is invasive to the UK and causing damage to native biodiversity, such as oyster reefs. It is also an established cell and developmental model system and hence is the perfect species in which to characterise the development of the neuroendocrine system of molluscs and test the effect of environmentally relevant pharmaceutical EDs.

PROJECT AIMS 1.) Characterise the development of the neuroendocrine system in molluscs

2.) Systematically test the effect of known environmentally relevant neuroendocrine disrupting chemicals (such as dutasteride) on developmental processes in molluscs 3.) Extrapolate the effects measured in individuals to impacts on populations