Chronic exposure to anthropogenic and climate related stressors alters transcriptional responses in the liver of zebrafish (Danio rerio) across multiple generations.

The antidepressant, venlafaxine (VFX), and climate change stressors, such as increased water temperature and decreased dissolved oxygen, are current threats to aquatic environments. This study aimed to determine how microRNAs (miRNAs) and predicted targeted transcripts were altered in livers of zebrafish exposed to these stressors, and livers of their un-exposed F 1 and F 2 offspring. Following a 21 day exposure to multiple stressors (1 μg/L VFX, +5 °C ambient, 50% O 2), then a subsequent 21 day recovery, relative abundances of cyp3a65 , hsp70 , hsp90 , and ppargc1a and miRNAs predicted to target them (miR-142a, miR-16c, miR-181c, and miR-129, respectively) were measured in the liver via quantitative PCR (RT-qPCR). There were significant decreases in miR-142a in the exposed F 0 generation and the exposed F 1 generation. While there were no changes detected in cyp3a65 relative abundance, there was a significant inverse relationship between cyp3a65 and miR-142a. Hsp70 expression significantly increased in the F 1 generation, which persisted to the F 2 generation and the relative abundance of hsp90 significantly increased in all generations. There was a significant reduction in miR-181c in the F 1 generation, but there was no significant relationship between miR-181c and hsp90. Finally, there was a significant decrease in ppargc1a relative abundance in the F 1 generation which was associated with an increase in miR-129. Combined, these results suggest that parental exposure to multiple, environmentally relevant stressors can confer transcriptional and epigenetic responses in the F 1 and F 2 generations, although identifying which stressor is a driving force becomes unclear. Unlabelled Image • Adult zebrafish were exposed to 21 days of +5 °C, hypoxia (50%), and 1 μg/L venlafaxine. • Zebrafish were returned to control conditions and bred to F 1 and F 2 generations. • Inverse relationships were found between miR-142a and cyp3a65 & miR-129 and ppargc1a. • Hsp70 and hsp90 were significantly increased in the F 1 and F 2 generations. • Multi-stressor exposure confers mRNA and microRNA changes in future generations. [ABSTRACT FROM AUTHOR]