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Physiologie de la réponse et de la tolérance immunes dans l'épididyme murin

Abstract : The epididymis, a key organ of male fertility, is the place of maturation and storage of sperm. However, the massive and late arrival of these cells at puberty, long after the setting of self-tolerance, makes them potential targets for the immune system which risks to destroy them. At the same time, the male genital tract, in contact with the external environment, is frequently challenged by ascending pathogens, which, if not controlled, impair fertility. Therefore, the epididymis must develop an efficient immune response against pathogens while establishing effective tolerance towards sperm. Alteration of this equilibrium is involved in 10 to 15% of male infertility cases. Nevertheless, the immune system of the epididymis has long been neglected compared to that of the testis, due to the common and admittedly mistaken idea that the testis conferred their immune protection to the whole genital tract. The work carried out during this PhD. aimed to strengthen the available knowledge on cellular and molecular actors involved in the maintenance of the immune balance in the murine epididymis. My first objective was to identify and quantify the mononuclear phagocyte and lymphocyte populations present, at steady state, in the tissue. I identified and located three lymphocyte populations never described in the murine epididymis. The rest of my work focused on Transforming growth factor-beta (TGF-β), whose signaling pathway is involved in sperm tolerance in mice, but, its receptors had not been fully described in the organ. We have shown that the three TGF-β isoforms and their receptors are differently expressed throughout the organ, suggesting various roles in epididymal physiology, in addition to sperm tolerance.These studies have shown the diverse potential mechanisms involved in epididymal immune balance and offer many avenues for research to improve treatments of male infertility of immunological origin.
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Allison Voisin. Physiologie de la réponse et de la tolérance immunes dans l'épididyme murin. Biologie de la reproduction. Université Clermont Auvergne [2017-2020], 2018. Français. ⟨NNT : 2018CLFAC102⟩. ⟨tel-02518837⟩



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