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Impact des processus métaboliques foeto-placentaires sur l'exposition foetale au bisphénol A

Abstract : Prenatal exposure to bisphenol A (BPA) is suspected to induce adverse effects later in life. In this context, the goal of this thesis was to evaluate the human fetal exposure to BPA. Using a pharmacokinetic (PK) approach, we showed that BPA glucuronide (BPAG), the main metabolite of BPA that remains trapped in the fetal compartment, is slowly eliminated through its back conversion into BPA. A humanized PK model developed from these data predicted steady BPAG fetal plasma concentrations of 40ng/L in late pregnancy, i.e. about 1000 folds higher than corresponding BPA concentrations. A proteomic analysis of fetal tissues has shown that equimolar BPAG or BPA fetal exposures trigger similar physiological shifts in the ovine model, suggesting that BPAG hydrolysis might expose fetal tissues to BPA at levels of functional significance. It is concluded that BPAG levels in human cord blood are relevant indicators of fetal exposure to BPA during late pregnancy and should be taken into account for risk assessment
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Glenn Gauderat. Impact des processus métaboliques foeto-placentaires sur l'exposition foetale au bisphénol A. Toxicologie et chaîne alimentaire. INSA de Toulouse, 2016. Français. ⟨NNT : 2016ISAT0013⟩. ⟨tel-02083736⟩

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