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Master Thesis

Évaluation de la toxicité des perturbateurs endocriniens dans le cerveau en développement : impacts cellulaires et épigénétiques

Abstract : Endocrine disruptors (EDs) are suspected to be involved in the development of neurodevelopmental disorders. To improve our understanding of their toxicity mechanisms in the immature brain and to identify biomarkers, organotypic cultures of brain sections from both sexes were treated for 5 days with two widespread EDs, bisphenol A (BPA) and mono (2-ethylhexyl) phthalate (MEHP). We show that Bdnf and Kcc2 expressions, analyzed by quantitative RT-PCR, are repressed by BPA (0.1 μM) in cultures derived from male mice only. This sexual dimorphism, already described in vivo, supports the validity of our model. In addition, MEHP (10 μM) modulates the expression of a pro-inflammatory cytokine and a myelination marker. The expression of Dnmt (DNA methyltransferases) is also disturbed, without any modification of methylation at the Bdnf locus. As molecular signatures of early exposures, epigenetic alterations may help understanding the delayed effects of EDs. Ultimately, this project could provide a suitable method for in vitro screening of various exposure conditions that would be a prerequisite for targeted in vivo toxicity studies, thus contributing to improved risk assessment related to EDs.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-03160786
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Submitted on : Friday, March 5, 2021 - 3:02:29 PM
Last modification on : Thursday, April 15, 2021 - 3:11:41 AM
Long-term archiving on: : Sunday, June 6, 2021 - 7:02:18 PM

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Margaux Sechet. Évaluation de la toxicité des perturbateurs endocriniens dans le cerveau en développement : impacts cellulaires et épigénétiques. Sciences du Vivant [q-bio]. 2020. ⟨dumas-03160786⟩

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