PUBLICATION
Cortisol disruption and transgenerational alterations in the expression of stress-related genes in zebrafish larvae following fluoxetine exposure
- Authors
- Vera-Chang, M.N., Moon, T.W., Trudeau, V.L.
- ID
- ZDB-PUB-190903-10
- Date
- 2019
- Source
- Toxicology and applied pharmacology 382: 114742 (Journal)
- Registered Authors
- Trudeau, V.L.
- Keywords
- Cortisol, Epigenetic, Fluoxetine, Gene Expression, Zebrafish
- MeSH Terms
-
- Animals
- Antidepressive Agents, Second-Generation/toxicity
- Female
- Fluoxetine/toxicity*
- Gene Expression Regulation, Developmental*
- Hydrocortisone/genetics
- Hydrocortisone/metabolism*
- Larva/drug effects
- Larva/genetics
- Larva/metabolism*
- Male
- Pregnancy
- Random Allocation
- Selective Serotonin Reuptake Inhibitors/toxicity
- Stress, Psychological/chemically induced*
- Stress, Psychological/genetics
- Stress, Psychological/metabolism*
- Water Pollutants, Chemical/toxicity
- Zebrafish
- PubMed
- 31476325 Full text @ Tox. App. Pharmacol.
- CTD
- 31476325
Citation
Vera-Chang, M.N., Moon, T.W., Trudeau, V.L. (2019) Cortisol disruption and transgenerational alterations in the expression of stress-related genes in zebrafish larvae following fluoxetine exposure. Toxicology and applied pharmacology. 382:114742.
Abstract
Fluoxetine (FLX), the active ingredient in well-known therapeutic drugs such as Prozac, is highly prescribed worldwide to treat affective disorders even among pregnant women and adolescents. Given that FLX readily crosses the placenta, a fetus from a treated pregnant woman is potentially at risk from unintended effects of the chemical. Moreover, FLX reaches aquatic ecosystems at biologically active levels through sewage release, so fish may also be inadvertently affected. We previously demonstrated that FLX exposure to environmentally- (Low FLX lineage; LFL) and human- (High FLX lineage; HFL) relevant concentrations during the first 6 days of life in zebrafish (ZF; Danio rerio) reduced cortisol levels in the adults (F0), an effect that persisted across 3 consecutive unexposed generations (F1 to F3). Here, we show that the transcriptional profile of selected genes in the steroidogenesis pathway in the F0 whole-larvae varied in magnitude and direction in both FLX lineages, despite the same attenuated cortisol phenotype induced by both concentrations. We also observed an up-regulation in the transcript levels of some steroidogenic-related genes and a down-regulation of a gene involved in the inactivation of cortisol in the F3 HFL larvae. These findings on the transcript levels of the selected genes in the larvae from F0 and F3 suggest that specific coping mechanism(s) are activated in descendants to attempt to counteract the disruptive effects of FLX. Our data are cause for concern, given the increasing prescription rates of FLX and other antidepressants, and the potential long-term negative impacts on humans and aquatic organisms.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping