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.

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Acquisition of iron is essential to several biochemical processes, including tricarboxylic acid cycle activity, respiration, antioxidant defense, and DNA replication (Galaris et al., 1866;Philpott et al., 2020;Puig et al., 2017). Iron plays a critical role as an electron transfer intermediate for catalytic enzyme activity due to its ability to lose or to gain one electron. On the other hand, when present in excess, iron in its reduced state can react with hydrogen peroxide to produce the highly toxic hydroxyl radical that can damage cellular components (Gutteridge & Halliwell, 2018). Consequently, cells have developed homeostatic mechanisms to acquire adequate, but not excessive, intracellular concentrations of iron.Studies in the model organism Schizosaccharomyces pombe have led to the identification of cellular components that are required to ensure adequate iron assimilation needed for some iron-dependent