La Dicarbonyl L-xylulose réductase (DCXR) dans l'épididyme : une enzyme, plusieurs fonctions
|Abstract:||The epididymis is a complex organ involved in spermatozoa maturation and acquisition of their fertilization abilities. The epididymis is segmented in different regions with specific gene expression patterns. DCXR gene, found in many species, is highly conserved during the evolution. The DCXR protein is involved in different biological processes of which, the inositol degradation energetic pathway. DCXR is highly expressed in the epididymis of studied species (mouse, hamster, monkey, human). In human, DCXR protein is found on the spermatozoa and is important for the binding of spermatozoa to the oocyte. The lack of this protein has been correlated with idiopathic infertility cases. We hypothesized that the high sequence homology of DCXR between species is associated with functionally conserved properties of the protein in mediating sperm-oocyte binding. We further hypothesized that the DCXR protein sequence contains specific functional domains that permit its multiple biological roles. We used the murine, human and bovine models for our studies. Bovine is a model in which the fertility can be quantified, what makes it interesting for the study of protein involved in fertilization. We report here the identification of DCXR in bull epididymis. The protein is highly expressed in the epididymis but shows expression and localization differences with the human counterpart. In the bovine epididymis, we identify the gene expression of enzymes involved in the inositol degradation metabolic pathway. The recombinant DCXR protein and the epididymis fluids xylitol dehydrogenase enzymatic activity, suggest the involvement of the protein in energy production by means of the inositol degradations pathway. By point mutations induction in the human DCXR, we revealed the protein domains involved in its enzymatic properties. Preliminary experiments did not conclusively demonstrate a role for DCXR during sperm-zona pellucida binding and a pilot test to create a DCXR-null animal model was unsatisfactory. Therefore, future research should focus on elucidating the function of this protein on male reproductive function. All together our results suggest a difference in the role of DCXR depending on the species studied.|
|Document Type:||Thèse de doctorat|
|Open Access Date:||23 April 2018|
|Collection:||Thèses et mémoires|
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