RT Journal Article
T1 Are fish populations at risk? Metformin disrupts zebrafish development and reproductive processes at chronic environmentally relevant concentrations
A1 Barros, Susana
A1 Alves, Nélson
A1 Pinheiro, Marlene
A1 Ribeiro, Marta
A1 Morais, Hugo
A1 Santos, Miguel M.
A1 Montes Goyanes, Rosa
A1 Coimbra, Ana M.
A1 Neuparth, Teresa
A1 Rodil Rodríguez, María del Rosario
A1 Quintana Álvarez, José Benito
K1 Contaminants of emerging concern
K1 Danio rerio
K1 Metformin full life cycle exposure
K1 Endocrine disruption
K1 Risk Assessment
K1 Water framework directive
K1 Watch List
AB The antidiabetic drug Metformin (MET), one of the most prevalent pharmaceuticals in the environment, is currently detected in surface waters in the range of ng/L to low μg/L. As current knowledge regarding the long-term effects of environmentally relevant concentrations of MET in nontarget organisms is limited, the present study aimed at investigating the generational effects of MET, in concentrations ranging from 390 to 14 423 ng/L in the model organism Danio rerio (up to 9 mpf), including the effects on its nonexposed offspring (until 60 dpf). We integrate several apical end points, i.e., embryonic development, survival, growth, and reproduction, with qRT-PCR and RNA-seq analyses to provide additional insights into the mode of action of MET. Reproductive-related parameters in the first generation were particularly sensitive to MET. MET parental exposure impacted critical molecular processes involved in the metabolism of zebrafish males, which in turn affected steroid hormone biosynthesis and upregulated male vtg1 expression by 99.78- to 155.47-fold at 390 and 14 432 MET treatment, respectively, pointing to an estrogenic effect. These findings can potentially explain the significant decrease in the fertilization rate and the increase of unactivated eggs. Nonexposed offspring was also affected by parental MET exposure, impacting its survival and growth. Altogether, these results suggest that MET, at environmentally relevant concentrations, severely affects several biological processes in zebrafish, supporting the urgent need to revise the proposed Predicted No-Effect Concentration (PNEC) and the Environmental Quality Standard (EQS) for MET
PB ACS
SN 0013-936X
YR 2022
FD 2022-12-29
LK http://hdl.handle.net/10347/31025
UL http://hdl.handle.net/10347/31025
LA eng
NO S. Barros et al. Environmental Science and Technology, 2023, 57, 1049-1059. https://doi.org/10.1021/ACS.EST.2C05719
NO This study was developed under the following projects: (1) 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], financed by the Portuguese Foundation for Science and Technology (FCT) and (2) Nor-Water – Pollutants of emerging concern in watersheds from Galicia-northern Portugal: new tools for risk management [Reference: 0725_NOR_WATER_1_P], financed by Programa de Cooperação Interreg Portugal/Espanha, (POCTEP) 2014–2020. The study was also supported by FCT under the projects [UIDB/04423/2020, UIDP/04423/2020, UIDB/04033/2020, and LA/P/0126/2020]. T.N. acknowledges FCT Individual Call to Scientific Employment Stimulus 2022 (2022.02925.CEECIND). S.B., M.P., H.M., N.A., and M.R. acknowledge FCT for their Ph.D. grants PD/BD/143090/2018, SFRH/BD/147834/2019, SFRH/BD/139762/2018, DFA/BD/6218/2020, and 2022.12763.BD, respectively. R.M. acknowledges Banco Santander and Universidade de Santiago de Compostela for her outstanding researcher contract. Financial support by Xunta de Galicia (ED431C 2021/06) and the Spanish Agencia Estatal de Investigación - MCIN/AEI/10.13039/501100011033 (PID2020-117686RB-C32) is also gratefully acknowledged.
DS Minerva
RD 24 abr 2026