Developmental exposure to the A6-pesticide causes changes in tyrosine hydroxylase gene expression, neurochemistry, and locomotors behavior in larval zebrafish

Abstract

Purpose: In recent years, the increase in the biopesticides synthesis for alternative agricultural uses has required their impacts study. Among these compounds, several of them are known to exert endocrinedisrupting (EDs) effects causing deregulation of physiological functions affecting cell signaling pathways involved in neural cell differentiation leading to developmental neurotoxicity. The objective of our study was to determine the impact of the biopesticide A6 structurally related to estrogenic EDs on zebrafish larvae, to define its toxicity, the mechanisms responsible, and to monitor the locomotors activity at nanomolar concentrations (0. 0.5, 5 and 50 nM).

Materials and methods: Using imaging analysis tools, immunohistochemistry, quantitative PCR, and an automated behavior recording system (Zebrabox) we were able to assess these effects.

Results: We have shown through its blue fluorescence properties that it accumulates in different parts of the body such as the intestine, adipose tissue, muscles, yolk sac and head. A6 also disrupted swimming behavior by affecting the expression of tyrosine hydroxylase (TH) in dopaminergic neurons.

Conclusions: In conclusion, our study provided a mechanistic understanding of the A6 neurotoxic effect which could be the result of its binding to the estrogen receptor.

Keywords:

• Zebrafish exposure
• malformations
• A6 accumulation
• tyrosine hydroxylase
• locomotors behavior

Acknowledgments

The authors extend their appreciation to INSERM (Institut National de la Santé et de la Recherche Médicale, France) for supporting several missions for Dr. Ahmed Nasri in Montpellier. We thank Elodie Jublanc and Vicky DIAKOU for help and training on SPE-confocal.

Ethical statements

This article was approved by INSERM and Montpellier University (agreement #A34-172-37, 10 April 2013).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was funded by Taif University Research through Project number (TURSP-2020/28), Taif University, Taif, Saudi Arabia.