Project description
Understanding the impact of endocrine disruptors on developmental health
The HYPIEND project aims to investigate the effects of multiple endocrine disruptor chemicals (EDCs) exposure on the function and epigenetic programming of the hypothalamus-pituitary (HP) axis. It foresees interventional strategies for minimising exposure and consequences on the neuroendocrine system during the perinatal, pre-pubertal stages. A computational toxicology framework will define the EDC co-exposure patterns to be evaluated in a sequential approach comprising cell-based screenings, Danio rerio models of HP axes, in vitro-silico-vivo models of placenta and blood brain barrier diffusion, and new models of organoids-based organ-on-a-chip. The EDC effects on epigenetic programming will be evaluated in preclinical models. Researchers will also explore genome DNA methylation patterns as a source of non-invasive biomarkers of HP axis disruption by EDCs. Controlled intervention studies will apply this knowledge to minimise the exposure.
Objective
Exposure to multiple endocrine disrupting chemicals (EDC) is an environmental insult that interferes with the development and function of the endocrine system, governed by the hypothalamus-pituitary (HP) axis. This interaction is specially concerning in developmental stages of life, such as the perinatal period and puberty. Despite the current body of knowledge on EDC actions on the endocrine system, a comprehensive, holistic understanding of the impact on the HP axis is still lacking. HYPIEND aims to understand the effects of EDC co-exposure in the function and epigenetic programming of the 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.
Fields of science
- natural sciencescomputer and information sciencesdata science
- medical and health sciencesclinical medicineobstetrics
- medical and health sciencesclinical medicineendocrinology
- engineering and technologyother engineering and technologiesmicrotechnologyorgan on a chip
- medical and health sciencesbasic medicinetoxicology
Keywords
Programme(s)
Funding Scheme
HORIZON-RIA - HORIZON Research and Innovation ActionsCoordinator
08290 Cerdanyola Del Valles (Barcelona)
Spain