Differential Hepatic Gene Expression Profile of Male Fathead Minnows Exposed to Daily Varying Dose of Environmental Contaminants Individually and in Mixture

Abstract

Environmental contaminants are known to impair reproduction, metabolism and development in wild life and humans. To investigate the mechanisms underlying adverse effects of contaminants, fathead minnows were exposed to a number of endocrine disruptive chemicals (EDCs) including Nonylphenol (NP), bisphenol-A (BPA), Di(2-ethylhexyl) phthalate (DEHP), and a mixture of the three chemicals for 21 days, followed by determination of the liver transcriptome by expression microarrays. Pathway analysis revealed a distinct mode of action for the individual chemicals and their mixture. The results showed expression changes in over 980 genes in response to exposure to these EDC contaminants individually and in mixture. Ingenuity Pathway core and toxicity analysis were used to identify the biological processes, pathways and the top regulators affected by these compounds. A number of canonical pathways were significantly altered, including cell cycle & proliferation, lipid metabolism, inflammatory, innate immune response, stress response, and drug metabolism. We identified 18 genes that were expressed in all individual and mixed treatments. Relevant candidate genes identified from expression microarray data were verified using quantitative PCR. We were also able to identify specific genes affected by NP, BPA, and DEHP individually, but were also affected by exposure to the mixture of the contaminants. Overall the results of this study provide novel information on the adverse health impact of contaminants tested based on pathway analysis of transcriptome data. Furthermore, the results identify a number of new biomarkers that can potentially be used for screening environmental contaminants.

Dietary diisononylphthalate contamination induces hepatic stress: a multidisciplinary investigation in gilthead seabream (Sparus aurata) liver

“…The results obtained in this study are in agree with previous research showing activation of hepatic stress response after EDCs exposure (Jin et al, 2010a;2010b;Zare et al, 2018). In particular, the modulation of antioxidant defence, the immune response and the possible onset of an apoptotic process were taken into consideration.…”

Bisphenol S leads to cytotoxicity-induced antioxidant responses and oxidative stress in isolated rainbow trout (Oncorhyncus mykiss) hepatocytes

“…Moreover, 12-24 h of incubation with BPA caused the upregulation of GSTM in another marine sh, Kryptolebias marmoratus [54]. Similar results were also reported as elevated GST speci c activity in the liver tissues of freshwater species like Pimephales promelas (Zare et al 2018) [55] and Oryzias latipes [56]. In the current study, BPS treatment of Oncorhyncus mykiss hepatocyte culture unveiled the very same response of elevated total GST speci c activity, demonstrating the practicality of the usage of this parameter in the testing of damage of xenobiotic exposure to aquatic animals.…”

Seasonally Related Disruption of Metabolism by Environmental Contaminants in Male Goldfish (Carassius auratus)

“…We have previously observed perturbations to male goldfish liver metabolism following EDC exposure alone and in mixture ( Jordan et al, 2012 ). Liver transcriptomics studies have shed light on alterations to lipid metabolism and the hepatic transcriptome following EDC exposure ( Santangeli et al, 2018 ; Zare et al, 2018 ). EDC alter neurotransmitter receptor pathways in brain as well as overall gene expression patterns ( Martyniuk et al, 2006 ; Gore, 2010 ) and polychlorinated biphenyls were observed to affect GnRH gene expression in GT-1 cell lines ( Gore, 2002 ).…”

“…In real-world exposure scenarios, both terrestrial and aquatic species are exposed to mixtures of contaminants, making results from individual exposure studies less applicable in modeling the extent of physiological perturbation induced by environmental contaminant exposures. Mixture studies are important as they more closely mimic the complexity of organisms responses to contaminants, and frequently show that the response is not simply additive ( Jordan et al, 2012 ; Kinch et al, 2015 ; Heys et al, 2016 ; Thrupp et al, 2018 ; Zare et al, 2018 ).…”