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Etude des mécanismes de transmission de dérégulations épigénétiques : analyse de la transmission spermatique chez l'homme

Abstract : The notion that environmental exposure can be memorized and promote epimutation (defined as defects on DNA methylation) raises the question of possible epigenetic transgenerational transmission in humans. To address whether an epimutation could be transmitted in humans, we pursued two axes. First, the evaluation of intergenerational transmission in the family of a Silver-Russell patient has shown, for the first time, the efficiency of epigenetic reprogramming in humans, specifically on imprinted regions. Indeed, no imprinted defect on causal H19/IGF2 locus was detected in the patient’s spermatozoa or in the DNA of his daughter. The second axis was to assess the presence of sperm epimutations 1/ from fathers of children diagnosed with imprinted syndromes and 2/ from men presenting testicular seminoma. Pyrosequencing analyses on imprinted genes did not reveal any alteration of sperm DNA methylation, though we confirmed an association between oligozoospermia and sperm imprinting defects.The next step will be to identify the mechanisms involved in the origin of the sperm epimutation. The main hypotheses converge to small non-coding RNAs or certain DNA regions which escape to controls setting up (at least partially) at the time of epigenetic reprogramming.
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Céline Bruno. Etude des mécanismes de transmission de dérégulations épigénétiques : analyse de la transmission spermatique chez l'homme. Médecine humaine et pathologie. Université Bourgogne Franche-Comté, 2018. Français. ⟨NNT : 2018UBFCI002⟩. ⟨tel-02119364⟩

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