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

Abstract 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 F1 and F2 offspring. Following a 21 day exposure to multiple stressors (1 μg/L VFX, +5 °C ambient, 50% O2), 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 F0 generation and the exposed F1 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 F1 generation, which persisted to the F2 generation and the relative abundance of hsp90 significantly increased in all generations. There was a significant reduction in miR-181c in the F1 generation, but there was no significant relationship between miR-181c and hsp90. Finally, there was a significant decrease in ppargc1a relative abundance in the F1 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 F1 and F2 generation, although identifying which stressor is a driving force becomes unclear.