Metabolomic Investigations of the Temporal Effects of Exposure to Pharmaceuticals and Personal Care Products and Their Mixture in the Eastern Oyster (Crassostrea virginica)

Abstract

The eastern oyster (Crassostrea virginica) supports a large aquaculture industry and is a keystone species along the Atlantic seaboard. Native oysters are routinely exposed to a complex mixture of contaminants that increasingly includes pharmaceuticals and personal care products (PPCPs). Unfortunately, the biological effects of chemical mixtures on oysters are poorly understood. Untargeted gas chromatography-mass spectrometry metabolomics was utilized to quantify the response of oysters exposed to fluoxetine, N,N-diethyl-meta-toluamide, 17α-ethynylestradiol, diphenhydramine, and their mixture. Oysters were exposed to 1 µg/L of each chemical or mixture for 10 d, followed by an 8-d depuration period. Adductor muscle (n = 14/treatment) was sampled at days 0, 1, 5, 10, and 18. Trajectory analysis illustrated that metabolic effects and class separation of the treatments varied at each time point and that, overall, the oysters were only able to partially recover from these exposures post-depuration. Altered metabolites were associated with cellular energetics (i.e., Krebs cycle intermediates), as well as amino acid metabolism and fatty acids. Exposure to these PPCPs also affected metabolic pathways associated with anaerobic metabolism, osmotic stress, and oxidative stress, in addition to the physiological effects of each chemical's postulated mechanism of action. Following depuration, fewer metabolites were altered, but none of the treatments returned them to their initial control values, indicating that metabolic disruptions were long-lasting. Interestingly, the mixture did not directly cluster with individual treatments in the scores plot from partial least squares discriminant analysis, and many of its affected metabolic pathways were not well predicted from the individual treatments. The present study highlights the utility of untargeted metabolomics in developing exposure biomarkers for compounds with different modes of action in bivalves. Environ Toxicol Chem 2020;39:419-436.

The Uptake of Ethinyl-Estradiol and Cortisol From Water by Mussels (Mytilus spp.)

“…This fact should not be surprising, as EE 2 has previously been detected in a gastropod snail ( 16 ) and specifically in mussels in at least three studies ( 17 – 19 ). Its uptake has also been demonstrated directly in two studies using either 14 C-radiolabelled ( 20 ) or non-radiolabelled ( 21 ) EE 2 .…”

“…This needs to be considered in any future studies on EE 2 depuration. A more recent study ( 21 ), is also highly relevant. When mussels were treated with cold EE 2 alone for 10 days, it was only detectable (as free EE 2 ) in the tissue on day 1.…”

1H-NMR metabolomics profiling of zebra mussel (Dreissena polymorpha): A field-scale monitoring tool in ecotoxicological studies

“…Metabolomics is a novel branch in ecotoxicology (Lin et al, 2006), and can be efficient to assess the health status of organisms by measuring small metabolites involved in different aspects of physiological processes (Brew et al, 2020;Nguyen and Alfaro, 2020). The production and levels of these metabolites can be modulated by physiological and/or environmental factors (Campillo et al, 2019;Cappello et al, 2013;Dumas et al, 2020;Lin et al, 2006).…”

Early Biological Modulations Resulting from 1-Week Venlafaxine Exposure of Marine Mussels Mytilus galloprovincialis Determined by a Metabolomic Approach

“…When M. galloprovincialis was exposed to polystyrene microplastics (PM) for 24, 48, and 72 h, detected AA tended to increase during the first two days of exposure and then decreased on the third day (BCAA, alanine, dimethylglycine, and tyrosine), whereas glycine levels (a glutathione constituent) steadily decreased over time [ 52 ]. When exposed to 1 µg/L FLX for 10 days, eastern oysters ( C. virginica ) also showed the same pattern for 6 AA (alanine, aspartate, isoleucine, proline, threonine, and valine) [ 53 ]. In our study, this trend was noted for 2 AA: L -phenylalanine increased at day 1 in male mussels and then decreased (+31% at day 1 and −31% at day 3, p < 0.05), while females reacted with up-modulation of L -lysine level on day 1 followed by a decrease at days 3 and 7 (respectively +39%, p > 0.1; −57% and −38%, p < 0.1).…”