Assessment of endocrine disruptors effects on zebrafish (Danio rerio) embryos by untargeted LC-HRMS metabolomic analysis

Abstract

Bisphenol A (BPA), perfluorooctane sulfonate (PFOS), and tributyltin (TBT) are emerging endocrine disruptors (EDCs) with still poorly defined mechanisms of toxicity and metabolic effects in aquatic organisms. We used an untargeted liquid chromatography-high resolution mass spectrometry (LC-HRMS) metabolomic approach to study the effects of sub-lethal doses of these three EDCs on the metabolic profiles of zebrafish embryos exposed from 48 to 120hpf (hours post fertilization). Advanced chemometric data analysis methods were used to reveal effects on the subjacent regulatory pathways. EDC treatments induced changes in concentrations of about 50 metabolites for TBT and BPA, and of 25 metabolites for PFOS. The analysis of the corresponding metabolic changes suggested the presence of similar underlying zebrafish responses to BPA, TBT and PFOS affecting the metabolism of glycerophospholipids, amino acids, purines and 2-oxocarboxylic acids. We related the changes in glycerophospholipid metabolism to alterations in absorption of the yolk sack, the main source of nutrients (including lipids) for the developing embryo, linking the molecular markers with adverse phenotypic effects. We propose a general mode of action for all three chemical compounds, probably related to their already described interaction with the PPAR/RXR complex, combined with specific effects on different signaling pathways resulting in particular alterations in the zebrafish embryos metabolism.

Embryotoxic and teratogenic effects of polyethylene microbeads found in facial wash products in Zebrafish (Danio rerio)using the Fish Embryo Acute Toxicity Test

“…Cases of mortality may be due to the soft extraction of polyethylene microbeads using 1% DMSO that may have induced leaching of toxic additives and Endocrine-Disrupting Chemicals (EDCs). In accordance with literature outside of this study, these leached chemicals may have disrupted metabolic pathways [5,85], alter gene integrity [85,86], and cause cell apoptosis [87]; hence possibly resulting in Danio rerio toxicity during embryogenesis; however, this needs a more thorough study at gene level. Adherence of polyethylene microbeads to the chorionic membrane may also have disrupted gas exchange and induced hypoxia [5].…”

“…Incidences of embryos exhibiting lack of somite formation and non-detachment of tail were observed in Danio rerio treated with PE-MBS (S2 Appendix) and may be attributed to chemical additives and EDCs added to pre-production polyethene microplastics [85]. Related literature outside of this study suggests that observed toxic endpoints related to somite defect may be associated with ectodermal implications during somitogenesis [91].…”

“…Another study by Rochman et al [3] stated that virgin pre-production polyethene microplastics contain Endocrine-Disrupting Chemicals (EDCs) such as bisphenol A (BPA). Aside from BPA being an exogenous compound that interferes with metabolic pathways and proper functioning of the endocrine system [5,85], accumulated evidence from past studies have ascertained that BPA is cytotoxic, have the ability to alter gene integrity [85,86] and induce cell apoptosis and organ necrosis to developing vertebrates [87]. In this study, 1% DMSO was used as a solubilizing agent to produce a suitable suspension for polyethylene microbeads [17].…”

Occurrence of selected endocrine disrupting compounds in the eastern cape province of South Africa

“…The presence of BPA in the midstream samples (BM, FM, SM and TM) of the rivers might result from a combination of waste dump, especially improperly disposed plastic packagings and runoff. Sub-lethal doses of bisphenol A in the aquatic environment have been shown to have adverse effects on the developing zebrafish embryos (Ortiz-Villanueva et al 2018). BPA has been implicated in infertility, obesity, cancer and neurologic impairments (Saal et al 2012;Itoh et al 2012 2014).…”

“…It may remain in the soil up to 4 years and might be washed to rivers or leached to groundwater where it degrades slowly (U.S. Environmental Protection Agency 2007). There are various reports of the effects of EDCs on wildlife, especially in freshwater ecosystems, such as abnormal development and death of embryos (Arukwe et al 2016;Ortiz-Villanueva et al 2018), changes in sexual behaviour (Kanda 2019), feminization of male animals (Carnevali et al 2018) and altered immune functions (Nowak et al 2019). The effects of EDCs had also been recorded in birds, especially those feeding in polluted waters (Roman et al 2019;Jessl et al 2018) and may ultimately lead to loss of biodiversity.…”