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Research strategy

The team's research strategy is based on a global approach integrating characterization and understanding :

•     The mechanisms of fetal exposure to these substances, in a context of chronic and low-dose exposure, specific to environmental or food contamination.
•     Their effects on the endocrino-metabolic and reproductive systems, following an adaptation of the organism to preserve its homeostasis.

The concepts of toxicokinetics/toxicodynamics (TK/TD) are thus applied to the model of the ovine fetus instrumented to analyze the relationship between maternal exposure to food contaminants and its effects through early markers of a disruption of endocrino-metabolic and reproductive functions.
The interest of toxicokinetic models is that they allow to simulate plasma concentrations of contaminants for different human exposure scenarios and to develop animal exposure patterns representative of human exposure for toxicological studies. The so-called toxicokinetic/toxicodynamic modeling of the relationship between systemic internal exposure to contaminants and their effects aims at predicting the effects of low-noise human exposure to contaminants.
Human biomonitoring data are used to validate TK models but also to develop population-based TK-TD approaches and to analyze the effects of exposure of women of childbearing age to contaminants on ovarian function.
The identification of the mechanisms that control exposure and effects is part of a remediation approach that aims to limit internal exposure and toxicological effects of contaminants. In this context, particular attention is paid to nuclear receptors including CAR (Constitutive Androstane Receptor) and PXR (Pregnane X Receptor) because of their involvement in many physiological processes including detoxification and lipid metabolism.

Some striking results

•     Predicted human fetal plasma concentrations of bisphenol A glucuronide (40ng/L) are stable and reflect the cumulative amount of bisphenol A to which the mother was exposed during pregnancy (https://www.nature.com/articles/s41598-017-15646-5).
•     The replacement of bisphenol A by bisphenol S leads to a very significant (X250) increase in plasma concentrations of active bisphenol (https://ehp.niehs.nih.gov/doi/10.1289/ehp4599).
•     The disruption of maternal thyroid function resulting from low-noise exposure to bisphenol A affects the metabolome of specific regions of the central nervous system of the fetal sheep.