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Theses

Effets biologiques et mécanismes d'action de ligands environnementaux du récepteur nucléaire de la progestérone chez le poisson zèbre

Abstract : Among vertebrates, progesterone (P4) is an endogenous progestin acting through the nuclear and molecular progesterone receptor to mediate key processes of development and reproduction. Many molecules are designed to mimic the action of P4. These synthetic progestins and P4 are widely used as pharmaceuticals and some of them are found in this aquatic environment, thus posing risks to aquatic species. However, information is lacking to evaluate the dangers and risks of these substances for the environment. This thesis studied the mechanisms of action and the effects of progestins on zebrafish, using a combination of reporter-gene in vitro and in vivo tools based on the mechanism of action of endocrine disruptors. We characterized the toxicological profile of 26 progestins towards different human and zebrafish nuclear steroid receptors and towards the tissue-specific expression of steroidogenic genes (cyp19a1b in the brain and cyp11c1 in the interrenal cells). Our results show that some progestins can disrupt different signaling pathways in developing larvae at the molecular level, cellular and tissular level, and physiological level. Overall, the results of this thesis allow for a better characterization of the dangers of progestins on several endocrine targets.
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https://tel.archives-ouvertes.fr/tel-01745554
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Submitted on : Wednesday, March 28, 2018 - 12:57:07 PM
Last modification on : Monday, January 27, 2020 - 2:29:39 PM
Long-term archiving on: : Thursday, September 13, 2018 - 9:29:44 AM

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  • HAL Id : tel-01745554, version 1

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Clémentine Garoche. Effets biologiques et mécanismes d'action de ligands environnementaux du récepteur nucléaire de la progestérone chez le poisson zèbre. Ecotoxicologie. Université Rennes 1, 2017. Français. ⟨NNT : 2017REN1B023⟩. ⟨tel-01745554⟩

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