HYPIEND

Understanding and preventing the impact of endocrine disruptors on the hypothalamus-pituitary axis in sensitive populations.

The HYPIEND project, coordinated by Eurecat, investigates the effects of multiple endocrine disrupting chemicals (EDC) exposure in the function and epigenetic programming of the hypothalamus-pituitary (HP) axis to delineate interventional strategies for minimizing exposure and consequences on the neuroendocrine system during the perinatal and pre-pubertal stages.

To do that, a computational toxicology methodological framework will be built leveraging public data and state of the art data analysis techniques to define EDC co-exposure patterns in target population.

The resulting patterns will be evaluated in a sequential tiered approach consisting in cell-based screenings, Danio rerio models of HP axes, in vitro, in silico and in vivo models of placenta and blood brain barrier diffusion and new models of organoids-based organ-on-chip recapitulating the HP axis.

EDC effects on epigenetic programming will be evaluated in preclinical models of perinatal and early childhood. Whole genome DNA methylation patterns in the different models will be explored as a source of non-invasive biomarkers of HP axis disruption by EDC.

The knowledge generated in preclinical models will be applied in two multi-centre-controlled intervention studies intended to minimize exposure to EDC in children in the perinatal and pre-puberty stages.

HYPIEND outcomes will be novel approach methodologies based in in vitro and in silico models, non-invasive biomarkers of HP disruption by EDC and new intervention strategies to minimize EDC exposure in sensitive population.

Eurecat leads the HYPIEND project and, through its Units of Nutrition and Health and Omic Sciences, takes charge of different tasks:

• Characterisation of EDC mixtures actions in whole genome methylation and release of extracellular vesicles in preclinical models.
• Study the effects of early life exposure to EDC mixtures on the HP axis in preclinical in vivo models.
• Definition of non-invasive effect biomarkers of HP axis disruption by genome methylation and circulating extracellular vesicles.
• Development of omics methodologies for discovery and characterization of biomarkers and EDC in biological samples.

The multidisciplinary HYPIEND consortium is made up of 14 partners from eight European countries.