Neuroendocrine pathways at risk? Simvastatin induces inter and transgenerational disruption in the keystone amphipod Gammarus locusta

The primary focus of environmental toxicological studies is to address the direct effects of chemicals on exposed organisms (parental generation - F0), mostly overlooking effects on subsequent non-exposed generations (F1 and F2 - intergenerational and F3 transgenerational, respectively). Here, we addressed the effects of simvastatin (SIM), one of the most widely prescribed human pharmaceuticals for the primary treatment of hypercholesterolemia, using the keystone crustacean Gammarus locusta. We demonstrate that SIM, at environmentally relevant concentrations, has significant inter and transgenerational (F1 and F3) effects in key signaling pathways involved in crustaceans' neumendocrine regulation (Ecdystemids, Catecholamines, NO/cGMP/PKG, GABAergic and Cholinergic signaling pathways), concomitantly with changes in apical endpoints, such as depressed reproduction and growth. These findings are an essential step to improve hazard and risk assessment of biological active compounds, such as SIM, and highlight the importance of studying the transgenerational effects of environmental chemicals in animals' neuroendocrine regulation.

Automated summary

The primary focus of environmental toxicological studies is often on the direct effects of chemicals on exposed organisms, while the effects on subsequent non-exposed generations are often overlooked. In this study, the effects of simvastatin on a keystone crustacean were investigated, and it was found that simvastatin at environmentally relevant concentrations has significant inter and transgenerational effects on the neuroendocrine regulation of crustaceans, leading to adverse effects on reproduction and growth.