A realistic mixture of ubiquitous persistent organic pollutants affects bone and cartilage development in zebrafish by interaction with nuclear receptor signaling

PLoS One. 2024 Mar 28;19(3):e0298956. doi: 10.1371/journal.pone.0298956. eCollection 2024.

Abstract

"Persistent organic pollutants (POPs)" have a plethora of deleterious effects on humans and the environment due to their bioaccumulative, persistent, and mimicking properties. Individually, each of these chemicals has been tested and its effects measured, however they are rather found as parts of complex mixtures of which we do not fully grasp the extent of their potential consequences. Here we studied the effects of realistic, environmentally relevant mixtures of 29 POPs on cartilage and bone development using zebrafish as a model species. We observed developmental issues in cartilage, in the form of diverse malformations such as micrognathia, reduced size of the Meckel's and other structures. Also, mineralized bone formation was disrupted, hence impacting the overall development of the larvae at later life stages. Assessment of the transcriptome revealed disruption of nuclear receptor pathways, such as androgen, vitamin D, and retinoic acid, that may explain the mechanisms of action of the compounds within the tested mixtures. In addition, clustering of the compounds using their chemical signatures revealed structural similarities with the model chemicals vitamin D and retinoic acid that can explain the effects and/or enhancing the phenotypes we witnessed. Further mechanistic studies will be required to fully understand this kind of molecular interactions and their repercussions in organisms. Our results contribute to the already existing catalogue of deleterious effects caused by exposure to POPs and help to understand the potential consequences in at risk populations.

MeSH terms

  • Animals
  • Environmental Pollutants* / toxicity
  • Humans
  • Persistent Organic Pollutants*
  • Tretinoin
  • Vitamin D
  • Zebrafish

Substances

  • Persistent Organic Pollutants
  • Environmental Pollutants
  • Tretinoin
  • Vitamin D

Grants and funding

This research was funded by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Innovative Training Network (ITN) program PROTECTED [Grant agreement No. 722634]. G.G-L. was a PROTECTED fellow, M.M. is a "Maître de Recherche" at "Fonds National de Recherche Scientifique (FNRS).