Transgenerational inheritance of chemical-induced signature: A case study with simvastatin
The hypothesis that exposure to certain environmental chemicals during early life stages may disrupt reproduction across multiple non-exposed generations has significant implications for understanding disease etiology and adverse outcomes. We demonstrate here reproductive multi and transgenerational effects, at environmentally relevant levels, of one of the most prescribed human pharmaceuticals, simvastatin, in a keystone species, the amphipod Gammarus locusta. The transgenerational findings has major implications for hazard and risk assessment of pharmaceuticals and other contaminants of emerging concern given that transgenerational effects of environmental chemicals are not addressed in current hazard and risk assessment schemes. Considering that the mevalonate synthesis, one of the key metabolic pathways targeted by simvastatin, is highly conserved among metazoans, these results may also shed light on the potential transgenerational effects of simvastatin on other animals, including humans. ; This research was funded by COMPETE 2020, Portugal 2020, the European Union through the ERDF and the Portuguese Foundation for Science and Technology – FCT (Transobesogen project – Trans-phyletic obesogenic responses: from epigenetic modules to transgenerational environmental impacts, reference: PTDC/CTA-AMB/31544/2017 – NORTE-01-0145-FEDER-031544). This research was also supported by the National Funds through FCT under the projects (UIDB/04423/2020; UIDP/04423/2020), by the Spanish Agencia Estatal de Investigación (CTM2017-84763-C3-2-R), and by the Galician Council of Culture, Education and Universities (ED431C2017/36), cofounded by ERDF. A PhD grant awarded to Susana Barros (PD/BD/143090/2018) was funded by the FCT ; SI