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

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.

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Topic(s)

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HORIZON-RIA - HORIZON Research and Innovation Actions

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Call for proposal

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(opens in new window) HORIZON-HLTH-2023-ENVHLTH-02

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Coordinator

FUNDACIO EURECAT
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 057 288,25
Address
AVENIDA UNIVERSITAT AUTONOMA 23
08290 Cerdanyola Del Valles (Barcelona)
Spain

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 057 288,25

Participants (11)

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