Titre
A transient postnatal exposure to xenoestrogens programs long- term cardiac alterations: Role of microRNAs
Type
mémoire de master/maîtrise/licence
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Auteur(s)
FROSSARD, M.-P.
Auteure/Auteur
Directrices/directeurs
SIMEONI, U.
Directeur⸱rice
SIDDEEK, B.
Codirecteur⸱rice
Liens vers les personnes
Liens vers les unités
Faculté
Université de Lausanne, Faculté de biologie et médecine
Statut éditorial
Accepté
Date de publication
2021
Nombre de pages
25
Langue
anglais
Résumé
A worldwide increase in the burden of non-communicable diseases with developmental origin, such as cardiovascular diseases, is currently observed. Epidemiological and experimental studies indicate that exposure to challenges during early developmental life increases the risk of developing non-communicable diseases later in life. Among these challenges, environmental toxicants, such as endocrine-disrupting chemicals, have been shown to have critical impact on lifelong health. However, the role of such early transient exposure on the heart is poorly studied. Therefore, using a model of rats exposed postnatally and transiently to estradiol benzoate (EB), we aimed at determining whether an early transient postnatal exposure to EDCs has effects on the
adult heart and at identifying the molecular mechanisms in cardiac pathogenesis.
We found that an early transient postnatal exposure to EB induced cardiac hypertrophy in adulthood. Prompting for a search of the underlying mechanisms, we highlighted a subset of micro-RNAs that were downregulated. Among the pathways predicted to be impacted by this modification, the RAS/MAPK signaling pathway was identified. To verify the impact of microRNA deregulation on this pathway, we measured the expression level of different proteins involved in this signaling and regulating critical cellular mechanisms in the heart such as cell survival. We thus highlighted decreased AKT levels, and increased Cleaved Caspase-3 levels in the adult heart of animals exposed postnatally to EB. We next evaluated the potential origins for such microRNAs downregulations and highlighted decreased DGCR8 expression, which could induce altered microRNAs biogenesis. Also, owing the fact that microRNAs maturation can be influenced by estrogens through estrogens receptors, we discovered that GPR30 and EGFR were both downregulated. In conclusion, our work highlighted the long-term programming of cardiac hypertrophy by an early and transient exposure to xenoestrogens and identified microRNAs
alteration as a potential underlying mechanism.
adult heart and at identifying the molecular mechanisms in cardiac pathogenesis.
We found that an early transient postnatal exposure to EB induced cardiac hypertrophy in adulthood. Prompting for a search of the underlying mechanisms, we highlighted a subset of micro-RNAs that were downregulated. Among the pathways predicted to be impacted by this modification, the RAS/MAPK signaling pathway was identified. To verify the impact of microRNA deregulation on this pathway, we measured the expression level of different proteins involved in this signaling and regulating critical cellular mechanisms in the heart such as cell survival. We thus highlighted decreased AKT levels, and increased Cleaved Caspase-3 levels in the adult heart of animals exposed postnatally to EB. We next evaluated the potential origins for such microRNAs downregulations and highlighted decreased DGCR8 expression, which could induce altered microRNAs biogenesis. Also, owing the fact that microRNAs maturation can be influenced by estrogens through estrogens receptors, we discovered that GPR30 and EGFR were both downregulated. In conclusion, our work highlighted the long-term programming of cardiac hypertrophy by an early and transient exposure to xenoestrogens and identified microRNAs
alteration as a potential underlying mechanism.
Sujets
PID Serval
serval:BIB_41CD0A2AD2F7
Date de création
2022-09-07T13:25:00.111Z
Date de création dans IRIS
2025-05-20T19:29:31Z
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Nom
Mémoire no 7935 Mme Frossard.pdf
Version du manuscrit
imprimatur
Taille
6.85 MB
Format
Adobe PDF
PID Serval
serval:BIB_41CD0A2AD2F7.P001
Somme de contrôle
(MD5):6bfb16d541f316f81d34e229158e0fe5