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icon-endocrine-disruption-assay Endocrine Disruption Assay

A large number of chemicals promote endocrine disruption. Their presence in our ecosystems has harmful consequences in animal and human reproductive performance and behavior. The assessment of this potential hazard is enforced by regulatory agencies. 

As recently published (1), zebrafish displays highly-conserved endocrine genetic pathways. This allows to use this model for addressing chemically-induced endocrine disruption with high-translatability in a 3Rs-compliant manner. 

Method description

The objective of this assay is to detect potential endocrine disrupting chemicals (EDCs) through gene expression biomarkers in zebrafish. 

Early-life zebrafish embryos are exposed to the molecule of interest and the three endocrine pathways are assessed individually or simultaneously through transcriptional analysis of a panel of 8 validated biomarkers (1). The disruption can be evaluated as activation or repression of the pathway.

Figure: method description of the transcriptional analysis

Readouts

Anti-/Estrogenicity

Dose-response expression of cyp19a1b and vtg1 genes.

Estrogenic control: 17β-estradiol. Anti-estrogenic control: Fulvestrant.

Estrogenic and androgenic disruption measured as fold induction compared to the control (E3 medium+DMSO). All biomarker genes were validated using EDC controls and selected through exposure to their natural ligands (17β-estradiol, testosterone or T3).

Anti-/Androgenicity

Dose-response expression of sult2st3 and cyp2k22 genes.

Androgenic control: Testosterone. Antiandrogenic controls: Vinclozolin, Nilutamide.

Thyroid disruption

Dose-response expression of tpo, ttr, trα and dio2 genes.

Thyroid control: 3,3′,5-triiodo-L-thyronine (T3).

References

  1. Jarque et al. Multiplex Analysis Platform for Endocrine Disruption Prediction using Zebrafish. Int. J. Mol. Sci. 2019, 20(7), 1739