About Us
Project execution
January 2024 - December 2028
Coordinator
Eurecat Technology Center
Duration
60 months
Budget
€ 6.694.438,25
ABOUT HYPIEND
Understanding and preventing the impact of endocrine disruptors on the hypothalamus-pituitary axis in sensitive populations
The HYPIEND project investigates the effects of multiple endocrine disrupting chemicals exposure on the function and epigenetic programming of the Hypothalamus-Pituitary (HP) axis. The main goal is to delineate interventional strategies for minimizing its 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 the target population.
The resulting patterns will be evaluated in a sequential (tiered) approach consisting in cell-based screenings, Danio rerio models of hypothalamus-pituitary 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. Whole genome DNA methylation patterns in different models will be explored as a source of non-invasive biomarkers of HP axis disruption by EDCs.
The knowledge generated in preclinical models will be applied in two multi-centre-controlled intervention studies intended to minimize exposure to EDCs pregnant women and their infants, and pre-pubertal children.
PROJECT OBJECTIVES
From novel methodologies to the deployment of innovative strategies to minimise EDCs risks
EXPECTED OUTCOMES
Improving public health and contributing to regulatory action
HYPIEND outcomes will include novel approach methodologies based in in vitro and in silico models, non-invasive biomarkers of hypothalamus – pituitary axis disruption by EDCs and new intervention strategies to minimize EDC exposure in sensitive populations.
By identifying and assessing the health risks associated with EDCs. This can help policymakers and healthcare professionals make informed decisions about how to reduce exposure to these chemicals and improve public health outcomes.
HYPIEND will raise consumer awareness about the potential risks associated with EDCs, helping consumers to make more informed purchasing decisions and advocate for safer products.
HYPIEND will help inform and shape government regulations and policies aimed at reducing exposure to these chemicals and protecting public health and the environment.
METHODOLOGY
Step-by-step holistic methodology
The project methodology incudes a sequence of tasks aimed at defining the impact of realistic co-exposure to EDCs on the hypothalamus – pituitary axis in target life stages
Data analytics
Data from public databases will be combined with computational approaches (such as QSAR methodology) to develop a knowledge base linking selected EDC exposure with health outcomes. Computational methodologies will be combined with data analysis to identify co-exposure patterns.
Laboratory studies
Candidate EDC mixtures will be tested in cell-based models to define dose-response patterns. Zebrafish models and models of placenta and blood brain barrier will be used, later assessed in organoids and Organoids-on-chip derived from stem cells. Laboratory animals will be exposed to EDC mixtures to assess the programming and cumulative effects of EDC exposure in HP axis.
Interventional studies
Associations between EDCs and HP-related effect will be explored in pregnant and breastfeeding women and children in their 1000 first days and pre-pubertal stages. Human studies have been conceived as novel interventions to promote decreases in EDC exposure and to assess the cause-effect relationship.
ABOUT ENDOCRINE DISRUPTORS
Endocrine disruptor chemicals interfere with the operation of the hormonal system
EDCs are chemicals that can interfere with the operation of the hormonal system, especially at critical developmental stages of life such as pregnancy, infancy, and childhood. Hormones are natural chemicals produced in cells within endocrine glands, which are located throughout the body.
EDCs are an exogenous [non- natural] chemical, or mixture of chemicals, that interferes with any aspect of hormone action.
They allow for development, adaptation, and maintenance of bodily processes and health, play key roles in determining quality of life, and many are essential for survival, according to the report “Endocrine Disrupting Chemicals: Threats to Human Health”, written by the Endocrine Society in collaboration with IPEN.
In this same report, issued in February 2024, it is elucidated that due to the crucial involvement of the endocrine system in numerous vital biological and physiological processes, disruptions in any aspect of this system can result in illness or potentially fatal outcomes. Exposure to EDCs can therefore disrupt various bodily functions by interfering with the endocrine systems.
HYPIEND project will specifically analyse EDCs impact on the hypothalamic-pituitary axis, a structure where the central nervous system and the endocrine system converge. This system regulates hormones such as the thyroid stimulating hormone (TSH), the growth hormone or oxytocin, which in turn coordinate body functions including somatic growth, lactation and coping with stress.
