Transcriptomic analysis of the impacts of ethinylestradiol (EE2) and its consequences for proliferative kidney disease outcome in rainbow trout (Oncorhynchus mykiss).

Freshwater fish are threatened by the cumulative impact of multiple stressors. The purpose of this study was to unravel the molecular and organism level reactions of rainbow trout, Oncorhynchus mykiss, to the combined impact of two such stressors that occur in the natural habitat of salmonids. Fish were infected with either the myxozoan parasite, Tetracapsuloides bryosalmonae, which causes proliferative kidney disease (PKD), or exposed to ethinylestradiol (EE2) an estrogenic endocrine disrupting compound, or to a combination of both (PKD × EE2). PKD is a slow progressive chronic disease here we focused on a later time point (130-day post-infection (d.p.i.)) when parasite intensity in the fish kidney has already started to decrease. At 130 d.p.i., RNA-seq technology was applied to the posterior kidney, the main target organ for parasite development. This resulted with 280 (PKD), 14 (EE2) and 444 (PKD × EE2) differentially expressed genes (DEGs) observed in the experimental groups. In fish exposed to the combination of stressors (PKD × EE2), a number of pathways were regulated that were neither observed in the single stressor groups. Parasite infection, alone and in combination with EE2, only resulted in a low intensity immune response that negatively correlated with an upregulation of genes involved in a variety of metabolic and inflammation resolution processes. This could indicate a trade-off whereby the host increases investment in recovery/resolution processes over immune responses at a later stage of disease. When PKD infection took place under simultaneous exposure to EE2 (PKD × EE2), parasite intensity decreased and pathological alterations in the posterior kidney were reduced in comparison to the PKD only condition. These findings suggest that EE2 modulated these response profiles in PKD infected fish, attenuating the disease impact on the fish. Crown