Effects of parental exposure to amitriptyline on the survival, development, behavior, and gene expression in zebrafish offspring

Abstract

In mammals, parental exposure to amitriptyline (AMI) has been proven to contribute to congenital disabilities in their offspring. However, no studies have paid attention to the adverse effects of parental exposure to amitriptyline on fish offspring. In this study, we exposed adult zebrafish (F0) to AMI (0.8 μg/L) for 21 days. Subsequently, these zebrafish (F0) were allowed to mate, and their offspring (F1) were collected to culture in clean water for 5 days. The mortality rate, average hatching time, and heart rate at 48 h post-fertilization (hpf) of F1 were investigated. Our results showed that parental exposure to AMI induced tachycardia and increased mortality in F1 zebrafish. Under a light/dark transition test, F1 larvae born from AMI-exposed parents exhibited lower locomotor activity in the dark period and decreased thigmotaxis in the light period. The transcriptome analysis showed that parental AMI exposure dysregulated some key pathways in their offspring. Through the prediction of key driver analysis, six differentially expressed genes (DEGs) were revealed as key driver genes involved in protein processing in endoplasmic reticulum (hspa5, hsp70.1, hsp90a), ribosome (rps27a) and PPAR signaling pathway (pparab and fabp2). Considering that the concentration of AMI residual components in natural water bodies may be over our test concentration (0.8 μg/L), our findings suggested that toxicity of parental exposure to the offspring of fish should receive greater attention.

Keywords: Antidepressant; Behavior responses; Key driver analysis; Parental exposure; Zebrafish.