Descrizione del progetto
Comprendere l’impatto degli interferenti endocrini sulla salute dello sviluppo
Il progetto HYPIEND si prefigge di studiare gli effetti esercitati dall’esposizione a più sostanze chimiche che fungono da interferenti endocrini sulla funzione e sulla programmazione epigenetica dell’asse ipotalamo-ipofisi. Il progetto prevede strategie di intervento per ridurre al minimo l’esposizione e le conseguenze sul sistema neuroendocrino durante la fase perinatale e quella pre-puberale. Un quadro di tossicologia computazionale definirà i modelli di co-esposizione alle sostanze chimiche che fungono da interferenti endocrini da valutare nell’ambito di un approccio sequenziale che comprende screening basati su cellule, modelli di Danio rerio di assi ipotalamo-ipofisi, modelli in vitro-silico-vivo di diffusione della placenta e della barriera ematoencefalica e nuovi modelli di organoidi basati sull’approccio «organ-on-a-chip». I ricercatori del progetto valuteranno gli effetti di tali sostanze sulla programmazione epigenetica in modelli preclinici, esplorando inoltre i modelli di metilazione del DNA genomico come fonte di biomarcatori non invasivi dell’alterazione dell’asse ipotalamo-ipofisi da parte di questi interferenti. Gli studi di intervento controllati svolti nell’ambito di HYPIEND applicheranno queste conoscenze per ridurre al minimo l’esposizione.
Obiettivo
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.
Campo scientifico
- 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
Parole chiave
Programma(i)
Meccanismo di finanziamento
HORIZON-RIA - HORIZON Research and Innovation ActionsCoordinatore
08290 Cerdanyola Del Valles (Barcelona)
Spagna