Developmental toxicity of glyphosate on embryo-larval zebrafish (Danio rerio)

Ecotoxicol Environ Saf. 2022 May 1:236:113493. doi: 10.1016/j.ecoenv.2022.113493. Epub 2022 Apr 7.

Abstract

Glyphosate (GLY) induces developmental toxicity in fish, but research on the toxicity mechanism is limited. In this study, zebrafish embryos were exposed for 120 hpf to 0.7, 7, and 35 mg L-1 GLY. The results show that GLY treatment induced developmental toxicity in the fish, including premature hatching, reduced heartbeats, pericardial and yolk sac oedema, swim bladder deficiency, and shortened body length, which was possibly due to a significantly decreased triiodothyronine (T3)/thyroxine (T4) ratio and the abnormal expression patterns of hypothalamic-pituitary-thyroid (HPT) (crh, tshβ, tr α, tr β, and t tr ) and growth hormone/insulin-like growth factor (GH/IGF) axis-related genes (gh, ghrα, ghrβ, igf1, igf1rα, and igf1rβ) in larvae exposed to GLY. In addition, GLY exposure altered the levels of SOD and CAT, increased ROS, promoted malondialdehyde (MDA) content, and significantly altered the levels of endoplasmic reticulum (ER) stress signalling pathway factors (perk, eif2α, gadd34, atf4, ire1α, xbp1, atf6, hspa5, and chop), suggesting that GLY treatment induced oxidative injury and ER stress in the larvae. Further research showed that treatment with a higher concentration of GLY upregulated the levels of iNOS, IL-1β, and TNF-α while inhibiting the expression of IL-10 and TGF-β, suggesting that GLY causes an inflammatory reaction in the larvae. In addition, we also found that apoptosis was induced in the larvae, which was determined by acridine orange staining and abnormal expression of p53, caspase-3, -8, and -9. Taken together, our results demonstrate that GLY exposure altered the T3/T4 ratio, disturbed the expression patterns of HPT and GH/IGF axis-related genes, and induced oxidative and ER stress, inflammatory reactions, and apoptosis in the zebrafish larvae. This investigation contributes to improved understanding of the developmental toxicity mechanism of GLY in fish.

Keywords: Developmental toxicity; Glyphosate; Mechanism; Zebrafish.

MeSH terms

  • Animals
  • Embryo, Nonmammalian
  • Endoribonucleases / metabolism
  • Glycine / analogs & derivatives
  • Glyphosate
  • Larva
  • Protein Serine-Threonine Kinases
  • Water Pollutants, Chemical* / metabolism
  • Water Pollutants, Chemical* / toxicity
  • Zebrafish* / metabolism

Substances

  • Water Pollutants, Chemical
  • Protein Serine-Threonine Kinases
  • Endoribonucleases
  • Glycine