A Realistic Mixture of Persistent Organic Pollutants Affects Zebrafish Development, Behavior, and Specifically Eye Formation by Inhibiting the Condensin I Complex.

Persistent organic pollutants (POPs) are posing major environmental and health threats due to their stability, ubiquity, and bioaccumulation. Most of the numerous studies of these compounds deal with single chemicals, although real exposures always consist of mixtures. Thus, using different tests, we screened the effects on zebrafish larvae caused by exposure to an environmentally relevant POP mixture. Our mixture consisted of 29 chemicals as found in the blood of a Scandinavian human population. Larvae exposed to this POP mix at realistic concentrations, or sub-mixtures thereof, presented growth retardation, edemas, retarded swim bladder inflation, hyperactive swimming behavior, and other striking malformations such as microphthalmia. The most deleterious compounds in the mixture belong to the per- and polyfluorinated acids class, although chlorinated and brominated compounds modulated the effects. Analyzing the changes in transcriptome caused by POP exposure, we observed an increase of insulin signaling and identified genes involved in brain and eye development, leading us to propose that the impaired function of the condensin I complex caused the observed eye defect. Our findings contribute to the understanding of POP mixtures, their consequences, and potential threats to human and animal populations, indicating that more mechanistic, monitoring, and long-term studies are imperative.