The endocrine system is extremely well preserved among vertebrates. Among the most well-preserved elements are the glands (thyroid, gonads, adrenals, etc.) and the integration of signals from most of these glands occurs in the hypothalamus and pituitary. Assessment of EDCs relies mainly on their action and consequences at the peripheral gland level. However, investigation of cellular and molecular modifications at the hypothalamic/pituitary level, and the associated neuroendocrine and behavioural consequences, should be studied in priority. Analysis of the hypothalamus and pituitary
at transcriptomic level will allow the identification of key regulators potentially conserved among vertebrates. The obtained data will allow proposing relevant biomarkers for EDC exposure that are common to several endocrine systems, thus potential MIEs of KEs that can be used in AOPs. The main objective of this project is to determine the cellular and molecular signature at the hypothalamic level for the neuroendocrine and behavioural effects of developmental exposure to Endocrine disrupting Compounds (EDCs) mixture in hypothalamic neurons derived from human iPSCs, and in vivo mouse and aquatic models. The newly identified biomarkers will be compared across species. This translational approach aims to consider the hypothalamus/pituitary, which are still underestimated levels of action, as the integrative centre that connects several neuroendocrine systems and endpoints. A cross-species comparison will be also performed between species used for human health and the environment. Biomarkers would also be used to refine the existing test guidelines to integrate the hypothalamic/pituitary level in risk assessment.
- Host Institution: Centre national de la recherche scientifique, France
- Lead Supervisor 1: Jean-Baptiste Fini, Muséum National d’Histoire Naturelle
- Lead Supervisor 2: Sakina Mhaouty-Kodja, Institut Biologie Paris Seine
- Subject area: Hypothalamus, cell culture, transcriptomics