ProtoQSAR in the HYPIEND project

Endocrine-disrupting chemicals (EDCs) are natural or synthetic substances capable of mimicking, blocking, or interfering with the normal functioning of the endocrine system.

This system, composed of glands distributed throughout the body, produces and releases hormones into the bloodstream. These hormones act as signaling molecules that regulate essential physiological processes such as growth, metabolism, neurological development, and reproduction.

EDCs can alter endocrine signaling even at very low concentrations. They are present in a wide range of everyday products, including:

Human exposure to these substances can occur continuously through ingestion, inhalation, or dermal absorption. This represents a growing challenge for public health, as well as for the regulatory and environmental assessment of emerging chemicals.

HYPIEND, coordinated by the Eurecat Technology Centre, is an international research initiative focused on studying the effects of EDCs on the hypothalamic–pituitary axis — a key component of the neuroendocrine system responsible for maintaining hormonal homeostasis and coordinating vital functions such as metabolism, reproduction, and stress response.

Funded by the European Union’s Horizon Europe programme, HYPIEND brings together scientific teams from Spain, the Netherlands, Belgium, Sweden, Poland, Italy, Switzerland, and the United Kingdom, and will run from 2024 to 2028.

The main goal of the project is to understand and prevent the effects of EDC exposure on the function and epigenetic programming of the hypothalamic–pituitary axis, with a special focus on pregnant women and their offspring — groups considered highly vulnerable due to the differentiation and hormonal maturation processes that occur during development.

Although the scientific community has already identified numerous effects of EDCs, the specific mechanisms through which they influence this neuroendocrine axis, as well as the long-term consequences of such alterations, remain largely unknown.

HYPIEND aims to bridge this knowledge gap through a multidisciplinary approach combining:

The results of HYPIEND will contribute to the development of new methods for detecting and assessing endocrine disruptors, as well as to the design of more effective prevention, regulation, and chemical risk management strategies. Ultimately, the project aims to protect vulnerable populations and promote a chemically safer environment for future generations.

ProtoQSAR plays an active role in HYPIEND, contributing to the creation and organization of the project’s knowledge base on endocrine disruptors — the HYPIEND Knowledge Base (HYPIEND KB). This database integrates experimental and bibliographic information from different external sources, as well as results generated within the project itself.

To complement the experimental data collected in the HYPIEND KB, ProtoQSAR has developed QSAR (Quantitative Structure–Activity Relationship) models to evaluate the interaction of various compounds with multiple endocrine receptors.

These predictive models make it possible to estimate the disruptive potential of compounds and prioritize those requiring more detailed experimental studies, thus optimizing the project’s resources.

Our work provides a more efficient, reproducible, and sustainable evaluation process, supporting both the preclinical research and clinical studies carried out within HYPIEND, and contributing to a better understanding and prevention of the effects of endocrine-disrupting chemicals.

This project has received funding from the European Union’s Horizon Europe research and innovation programme (Innovation Action) under grant agreement No. 101137440.

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