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

T Neuparth; N Alves; A M Machado; M Pinheiro; R Montes; R Rodil; S Barros; R Ruivo; L Filipe C Castro; J B Quintana; M M Santos

doi:10.1016/j.aquatox.2022.106095

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

Aquat Toxicol. 2022 Mar:244:106095. doi: 10.1016/j.aquatox.2022.106095. Epub 2022 Jan 25.

Authors

T Neuparth¹, N Alves², A M Machado², M Pinheiro², R Montes³, R Rodil³, S Barros⁴, R Ruivo⁵, L Filipe C Castro², J B Quintana³, M M Santos⁶

Affiliations

¹ CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Avenida General Norton de Matos, S/N, 4450-208 Matosinhos, Portugal. Electronic address: tneuparth@ciimar.up.pt.
² CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Avenida General Norton de Matos, S/N, 4450-208 Matosinhos, Portugal; FCUP - Department of Biology, Faculty of Sciences, University of Porto, Porto, Portugal.
³ Department of Analytical Chemistry, Nutrition and Food Sciences, IAQBUS - Institute of Research on Chemical and Biological Analysis, Universidade de Santiago de Compostela, R. Constantino Candeira S/N, 15782 Santiago de Compostela, Spain.
⁴ CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Avenida General Norton de Matos, S/N, 4450-208 Matosinhos, Portugal; CITAB - Centre for the Research and Technology of Agro-Environmental and Biological Sciences, Quinta de Prados - Ed. Blocos Laboratoriais C1.10, 5000-801, Vila Real, Portugal.
⁵ CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Avenida General Norton de Matos, S/N, 4450-208 Matosinhos, Portugal.
⁶ CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Avenida General Norton de Matos, S/N, 4450-208 Matosinhos, Portugal; FCUP - Department of Biology, Faculty of Sciences, University of Porto, Porto, Portugal. Electronic address: miguel.santos@fc.up.pt.

PMID: 35121565
DOI: 10.1016/j.aquatox.2022.106095

Abstract

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' neuroendocrine regulation (Ecdysteroids, 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.

Keywords: Gammarus locusta; Inter and transgenerational effects; Neuroendocrine signaling pathways; Regulatory agencies; Simvastatin; Transcriptomic.

MeSH terms

Amphipoda*
Animals
Reproduction
Simvastatin / toxicity
Water Pollutants, Chemical* / toxicity

Substances

Water Pollutants, Chemical
Simvastatin