resumo
In this study, untargeted Nuclear Magnetic Resonance (NMR) metabolomics was applied for the first time, to our knowledge, to assess the metabolic impact of direct and transgenerational exposure (F0 and F3 generations, respectively) of amphipods Gammarus locusta to simvastatin (SIM), a pharmaceutical widely prescribed for the treatment of hypercholesterolemia. Results revealed the important gender-dependent nature of each of these effects. Directly exposed males showed enhanced glucose catabolism and tricarboxylic acid (TCA) cycle activity, in tandem with adaptations in osmotic regulation and glyoxylate metabolism. Exposed females exhibited only a small osmoregulatory effect. It is suggested that the response of exposed males may reflect reported high levels of methyl farnesoate hormone (low levels in females) and alterations in apical factors, namely decreased growth. Conversely, transgenerational effects were identified only in females, with impact on energy metabolism (glycolysis and TCA cycle enhancement) and osmoregulatory response. This expresses the ability of female gametes to transmit the effects of direct SIM exposure. Such effects were putatively related to reported delayed maturation and transcriptomic deviations impacting on carbohydrate and lipid metabolisms, possibly specifically engaging phenylalanine/tyrosine and choline in dopamine and choline metabolisms. These findings reflect the importance of untargeted metabolomics in addressing not only direct exposure of contaminants, but also their transgenerational effects, potentially contributing towards improving hazard and risk assessment of biologically active compounds.
autores
João A. Rodrigues; Raquel S. Chaves; Miguel M. Santos; Teresa Neuparth; Ana M. Gil
nossos autores
Projectos
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)
agradecimentos
The authors acknowledge TRANSEPIC − Exploring Transgenerational Epigenetic Inheritance: New Methods and Strategies to Improve Environmental Hazard and Risk Assessment of Key Contaminants of Emerging Concern (CECs) [Reference: 2022.02922.PTDC, 10.54499/2022.02922.PTDC], financed by the Portuguese Foundation for Science and Technology (FCT). This work was also developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 (10.54499/UIDB/50011/2020), UIDP/50011/2020 (10.54499/UIDP/50011/2020) & LA/P/0006/2020 (10.54499/LA/P/0006/2020), financed by national funds through the FCT/MCTES (PIDDAC). The NMR spectrometer is part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project N° 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). T.N. acknowledges FCT Individual Call to Scientific Employment Stimulus 2022 (2022.02925.CEECIND/CP1728/CT0004, 10.54499/ 2022.02925.CEECIND/CP1728/CT0004).