Zebrafish exposed to a cocktail of pesticides during early development display long-lasting neurobehavioral alterations

Arch Toxicol. 2025 Oct;99(10):4181-4195. doi: 10.1007/s00204-025-04129-6. Epub 2025 Aug 25.

Abstract

The widespread use of pesticides is increasing the presence of environmental contaminants with potential impacts on biodiversity, ecosystems, and human health. Although long-term pesticide effects have been previously studied, the long-term impact of an acute pesticide exposure during critical early developmental periods remains poorly understood. Here, we used zebrafish to examine whether acute exposure to a pesticide mixture at 0.5 μg/L (the maximum allowed in drinking water) during the first 5 days post-fertilisation (dpf) of development has lasting effects at 28 dpf. Zebrafish were assessed behaviourally, morphologically, and molecularly both immediately after exposure at 5 dpf and later at 28 dpf. Our results show alterations in stress-response that start to emerge right after the developmental exposure and are associated with a less anxious-like phenotype at juvenile stages. Interestingly, despite the observed behavioural phenotype at 28 dpf, it did not lead to significant molecular changes in the hypothalamic-pituitary-interrenal (HPI) axis at this stage. On the contrary, a positive control group of juvenile fish subjected to a sustained pesticide exposure throughout the 28 dpf showed both reduced anxiety-like behaviour and HPI alterations. Our study suggests that even an acute exposure to a low-concentration of pesticides during critical developmental periods can result in enduring behavioural changes.

Keywords: Agrochemical; Critical period; Early development; HPI axis; Pesticide; Stress-reactivity.

MeSH terms

  • Animals
  • Anxiety / chemically induced
  • Behavior, Animal* / drug effects
  • Hypothalamo-Hypophyseal System / drug effects
  • Pesticides* / toxicity
  • Water Pollutants, Chemical* / toxicity
  • Zebrafish* / growth & development
  • Zebrafish* / physiology

Substances

  • Pesticides
  • Water Pollutants, Chemical