4.8 Article

Transgenerational inheritance of chemical-induced signature: A case study with simvastatin

Journal

ENVIRONMENT INTERNATIONAL
Volume 144, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.envint.2020.106020

Keywords

Simvastatin; Transgenerational effects; Reproduction; Transcriptomic; Epigenetics; Regulatory agencies

Funding

  1. COMPETE 2020
  2. Portugal 2020
  3. European Union through the ERDF
  4. Portuguese Foundation for Science and Technology -FCT (Transobesogen project -Trans-phyletic obesogenic responses: from epigenetic modules to transgenerational environmental impacts) [PTDC/CTA-AMB/31544/2017 NORTE-01-0145-FEDER-031544]
  5. FCT [UIDB/04423/2020, UIDP/04423/2020, PD/BD/143090/2018]
  6. Spanish Agencia Estatal de Investigacion [CTM2017-84763-C3-2-R]
  7. Galician Council of Culture, Education and Universities [ED431C2017/36]
  8. ERDF
  9. Fundação para a Ciência e a Tecnologia [PD/BD/143090/2018] Funding Source: FCT

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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.

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