A transient postnatal exposure to xenoestrogens programs long- term cardiac alterations: Role of microRNAs

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Serval ID
serval:BIB_41CD0A2AD2F7
Type
A Master's thesis.
Publication sub-type
Master (thesis) (master)
Collection
Publications
Institution
Title
A transient postnatal exposure to xenoestrogens programs long- term cardiac alterations: Role of microRNAs
Author(s)
FROSSARD M.-P.
Director(s)
SIMEONI U.
Codirector(s)
SIDDEEK B.
Institution details
Université de Lausanne, Faculté de biologie et médecine
Publication state
Accepted
Issued date
2021
Language
english
Number of pages
25
Abstract
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.
Keywords
Endocrine-disrupting chemicals, postnatal, heart, microRNAs, cell survival
Create date
07/09/2022 14:25
Last modification date
13/09/2023 5:57
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