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Theses

Qualité du protéome du spermatozoïde humain et infertilité

Abstract : Motility is a key function of the fertilizing quality and the selection of sperm for assisted reproductive technology (ART). However, we lack information on molecular mechanisms controlling this mobility. This thesis is structured around 2 proteins of interest involved in sperm mobility: Tau (tubule-associated unit) associated with microtubule polymerization in the neuron, and the A-kinase anchoring protein 4 (AKAP4), the main protein of the fibrous sheath of the sperm’s flagellum, known for its involvement in sperm motility.Very few studies focus on the Tau protein in the male reproductive system, and none in humans. In the first part of this work, we analysed the expression of the Tau protein in the sperm and human testis through an immuno-histo-chemical approach (Article 1). The Tau protein is localized in the intermediate part of the sperm flagellum and in the spermatocyte and spermatid in the testis. The potential roles of the Tau protein during spermatogenesis are discussed in a review of the literature (Article 2).Advances in the field of proteomics now allow the study the proteome of sperm and its cellular compartments in a highly-resolutive way. The global sperm proteome was studied in men visiting the assisted reproduction center of Lille University Hospital. This has led to a group of sperm with predominantly high molecular weight proteins being identified as well as a group having proteolysis at the expense of high molecular weight proteins. The AKAP4 was identified among the high molecular weight proteins. We studied, quantified the profile of AKAP4 expression by Western Blot in the sperm of men undergoing a semen analysis and correlated the biochemical data of the proteome and AKAP4 to the semen analysis (article 3 in submission). The role of AKAP4 as a predictive marker of ART success is then discussed. Clinical and biological data (INFOFIV software) of ART attempts at the Lille University Hospital were compared with quantitative data of the global proteome and AKAP4 (Article 4 in preparation).Tau protein and AKAP4 are proteins of interest in the management of infertile men. The AKAP4 could be proposed as a biomarker in ART treatments.
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Julien Sigala. Qualité du protéome du spermatozoïde humain et infertilité. Médecine humaine et pathologie. Université du Droit et de la Santé - Lille II, 2016. Français. ⟨NNT : 2016LIL2S039⟩. ⟨tel-01673806v2⟩

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