Abstract
Acetaminophen (ACE; paracetamol) is one of the most widely used nonsteroidal anti-inflammatory drugs worldwide and is often found in aquatic systems, where it can act on nontarget species and impair fish reproduction. This study aimed to investigate the effects of chronic exposure to environmentally relevant ACE concentrations (0.5, 5 and 50 µg/L) on multiple reproductive parameters in zebrafish (Danio rerio). Gametogenesis was analyzed using histology, morphometry, cell proliferation, and apoptosis. This study also evaluated sex steroids, and prostaglandin E2 (PGE2) levels, gene expression for sex steroids and PGE2 receptors, fertilization rate, and semen quality. In females, exposure to 5 and 50 µg/L ACE induced larger and more abundant vitellogenic follicles and increased follicular atresia. In these treatments, males showed a lower proportion and proliferation of undifferentiated spermatogonia and a higher proportion of TUNEL-positive differentiated spermatogonia, spermatids, and spermatozoa, resulting in lower sperm production. ACE increased 17β-estradiol (E2) and reduced 11-ketotestosterone levels in the testis, whereas only E2 increased in the ovaries. In both sexes, gonadal PGE2 levels were reduced. ACE at 50 µg/L induced an increase in the gene expression of androgen, estrogen, and PGE2 receptors in the ovaries, and reduced expression in the testes. Results also showed lower egg production and fertilization rate from 28 days of exposure with reduced sperm quality. These results demonstrated that ACE impairs the reproductive performance of zebrafish, affecting multiple reproductive parameters, which may be caused by the synergistic action of the imbalance of sex steroids, with a reduction of PGE2 and its receptors.
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Acknowledgements
This study was supported by the following Brazilian institutions: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 310283/2020-5), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, financial code 001) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG). The authors would like to thank Adriana Raabe and the Proteomics Laboratory (ICB/UFMG) for their support in carrying out the water analyses, and Professor Gustavo Batista de Menezes and the team at the Center for Gastrointestinal Biology (ICB / UFMG) for their support in qPCR analyses.
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The authors declare their consent to have their names included in this study. DPM: conceptualization, methodology, data curation, formal analysis, writing, review, editing, YMR, CSF, SMSNL: methodology, data curation, review; ER: conceptualization, supervision, funding acquisition, writing, review, and editing. All authors performed data interpretation.
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Moreira, D.P., Ribeiro, Y.M., Ferreira, C.S. et al. Exposure to acetaminophen impairs gametogenesis and fertility in zebrafish (Danio rerio). Arch Toxicol 97, 263–278 (2023). https://doi.org/10.1007/s00204-022-03390-3
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DOI: https://doi.org/10.1007/s00204-022-03390-3