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Theses

Impact du stress oxydant sur l'intégrité de l'épigénome spermatique murin

Abstract : In Mammals, the success of fertilization and embryonic development, are associated to the quality of the reproductive cells: male gametes (spermatozoa) and female gametes (oocytes); each bringing half of the genetic heritage of the future individual. This genetic heritage may be compromised by various processes a very common one being radical attacks in cases of oxidative stress, it could diminish the quality of gametes and therefore the success of reproduction. It is well described that sperm DNA oxidative damage (SDOD) is one of the causes of male infertility frequently associated with reproductive failures in the context of natural or artificial conception in humans. To better understand the impact of oxidative damage on the quality of sperm, our team generated mouse models with SDOD. Characterization of these transgenic mice has shown that SDOD alone was associated with increased embryo defects, miscarriages and perinatal mortality. The team also brought forward that SDOD concerns preferentially specific regions of the sperm nucleus. In addition, the team suggested that sperm chromosomes were not identically susceptible to oxidative damage.In this thesis work, I developed and implemented fluorescence in situ hybridization (FISH) protocols to study chromosome positioning in the mouse sperm. I confirmed that susceptibility of chromosomes to oxidation is determined by their position in the murine sperm nucleus. In parallel, I addressed the question whether the sperm epigenome (particularly DNA methylation) was modified in a situation of post-testicular oxidative stress. Preliminary results seem to show that SDOD disturbs the sperm epigenetic profile.In parallel, in a pre-clinical approach, I contributed to show that an oral antioxidant supplementation can correct SDOD by modifying the antioxidant response of the epididymal tissue of the treated animals.
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https://tel.archives-ouvertes.fr/tel-01818050
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Submitted on : Monday, June 18, 2018 - 4:20:11 PM
Last modification on : Tuesday, January 15, 2019 - 3:03:37 PM
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Alexandre Champroux. Impact du stress oxydant sur l'intégrité de l'épigénome spermatique murin. Génétique. Université Clermont Auvergne, 2018. Français. ⟨NNT : 2018CLFAC004⟩. ⟨tel-01818050⟩

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