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Transgenerational inheritance of chemical-induced signature: A case study with simvastatin
Highlights We investigated the transgenerational effects of simvastatin (SIM) in Gammarus locusta. We reported reproductive transgenerational effects of SIM at environmentally levels. The reproductive impact was related with reduced levels of femaleś methyl farnesoate. SIM modulated key signalling pathways potentially linked with the reproductive effects. The transgenerational heritance has implications for risk assessment of pharmaceuticals.
Abstract 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.
Transgenerational inheritance of chemical-induced signature: A case study with simvastatin
Highlights We investigated the transgenerational effects of simvastatin (SIM) in Gammarus locusta. We reported reproductive transgenerational effects of SIM at environmentally levels. The reproductive impact was related with reduced levels of femaleś methyl farnesoate. SIM modulated key signalling pathways potentially linked with the reproductive effects. The transgenerational heritance has implications for risk assessment of pharmaceuticals.
Abstract 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.
Transgenerational inheritance of chemical-induced signature: A case study with simvastatin
Neuparth, T. (author) / Machado, A.M. (author) / Montes, R. (author) / Rodil, R. (author) / Barros, S. (author) / Alves, N. (author) / Ruivo, R. (author) / Castro, L. Filipe C. (author) / Quintana, J.B. (author) / Santos, M.M. (author)
2020-07-28
Article (Journal)
Electronic Resource
English
Simvastatin , Transgenerational effects , Reproduction , Transcriptomic , Epigenetics , Regulatory agencies , AACT , acetoacetyl-CoA thiolase , chiA , chitinase , CYP clan 2 , steroidogenic CYP (CYP 2L1) , ELOVL6 , elongation of very long chain fatty acids protein 6 , ELOVL7 , elongation of very long chain fatty acids protein 7 , FALD , farnesal dehydrogenase , FAMET , farnesoic acid O-methyltransferase , FOLD , farnosol dehydrogenase , FPPP , farnesyl diphosphate pyrophosphatase , FPPS , fanesyl diphosphate synthase , HEXA-B , hexosaminidase , HMGR , hydroxymethylglutaryl-CoA reductase , HMGS , hydroxymethylglutaryl-CoA synthase , IDI1 , isopentenyl diphosphate isomerase , JHAMT , juvenile hormone acid methyltransferase , JHEH , juvenile hormone epoxide hydrolase , LSS , lanosterol synthase , MDC , mevalonate-5-decarboxylase , MFE , methyl farnesoate epoxidase , MUFA , monounsaturated fatty acids , MVK , mevalonate kinase , PFK , 6-phosphofructokinase 1 , PUFA , Polyunsaturated fatty acids , PVK , phosphomevalonate kinase , SCD , stearoyl-CoA desaturase , SFA , Saturated fatty acids , SQLE , squalene monooxygenase , SQS , squalene synthase , SORD , L-iditol 2-dehydrogenase , UGT , glucuronosyltransferase , xylA , xylose isomerase
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