Publications (19) View all
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Article: [Post-testicular protection of male gametes from oxidative damage. The role of the epididymis].
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ABSTRACT: Spermatozoa leave the testis in an immature functional state and are devoid of self defense mechanisms. They will become motile and ready to fertilize only after their descent and their progressive maturation within the epididymal tubule. The epididymis also ensures the survival and the protection of male gametes while they go through the epididymis and during their storage in between two ejaculations. Amongst common stresses that concern spermatozoa, oxidative stress occupies a peculiar and dual position. While the events of epididymal sperm maturation necessitate a given level of oxidation, spermatozoa are particularly sensitive to oxidative damage. A fine balance between beneficial oxidation versus detrimental oxidative damage has to be maintained in the epididymal environment. Antioxidant enzymes of the glutathione peroxidase family play a key role in controling such a situation in the epididymis.Medecine sciences: M/S 05/2012; 28(5):519-25. · 0.64 Impact Factor -
Article: Rôle des récepteurs nucléaires des oxystérols LXR dans la régulation de l’homéostasie du cholestérol au niveau de l’appareil reproducteur mâle
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ABSTRACT: Les récepteurs nucléaires des oxystérols LXR (Liver X receptor) α et LXRß sont des facteurs de transcription appartenant à la superfamille des récepteurs nucléaires. Ils sont activés par une série particulière d’oxystérols. Des antagonistes naturels ont été également identifiés comme les acides gras poly-insaturés ou certains sulfates de cholestérol plasmatiques. L’étude des souris déficientes en LXRs a permis de les associer à la régulation de nombreux métabolismes (cholestérol, acides gras, glucose, stéroïdes). Les LXRs et leur partenaire RXR (récepteur de l’acide rétinoïque 9-cis) sont exprimés dans le tractus génital mâle et les testicules, et leurs ligands y sont à des concentrations physiologiquement actives. Dans ces organes, l’homéostasie du cholestérol doit être strictement régulée car 1) le cholestérol est un précurseur indispensable pour la synthèse des stéroïdes testiculaires; 2) pendant la maturation épididymaire, la membrane plasmique des spermatozoïdes subit des changements de composition notamment la diminution de cholestérol et de lécithines. L’analyse des souris déficientes en récepteurs LXR α et LXRß a mis en évidence une déstructuration de la couche épithéliale du segment 2 de la tête de l’épididyme, ainsi qu’une fragilité des spermatozoïdes recueillis. Au total, les analyses de physiologie intégrative et moléculaire mettent en évidence le rôle des récepteurs nucléaires LXRs dans la physiologie de la reproduction chez le mâle. Nuclear oxysterol receptors, LXRα and LXRß, are transcription factors that belong to the nuclear receptor superfamily. They bind and are activated by a specific class of oxysterols. Natural antagonists have also been described, such as polyunsaturated fatty acids or plasma sulfated oxysterols. Phenotypic analysis of mice lacking LXRα and/or LXRß demonstrated their roles in various physiologic processes and metabolisms (lipid or glucose homeostasis). LXR, as well as their heterodimeric partner RXR, the nuclear receptor for 9-cis retinoic acid, were shown to be expressed in male genital tracts and testes, and their respective ligands were found at physiologically active concentrations. In these organs, cholesterol homeostasis must be strictly regulated, as: 1) cholesterol is involved in androgen synthesis, and 2) during epididymal maturation of spermatozoa, the plasma membrane undergoes various modifications, mainly exchanges between cholesterol and phospholipids. We recently described that knock-out mice for both LXR encoding genes presented structural abnormalities of the epithelium of the head of the epididymis. These mice also presented fragile spermatozoa. Integrative and molecular physiology studies demonstrate a new role of these nuclear receptors in male reproductive physiology.Andrologie 04/2012; 15(2):151-159. -
Article: Correction: Epididymis Response Partly Compensates for Spermatozoa Oxidative Defects in snGPx4 and GPx5 Double Mutant Mice.
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ABSTRACT: [This corrects the article on p. e38565 in vol. 7.].PLoS ONE 01/2012; 7(9). · 4.09 Impact Factor -
Article: Glutathione peroxidases at work on epididymal spermatozoa: an example of the dual effect of reactive oxygen species on mammalian male fertilizing ability.
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ABSTRACT: The mammalian glutathione peroxidase (GPx) gene family encodes bifunctional enzymes that can work either as classical reactive oxygen species (ROS) scavengers or as thiol peroxidases, thereby introducing disulfide bridges in thiol-containing proteins. These dual effects are nowhere better demonstrated than in epididymal maturing spermatozoa, where the concomitant actions of several GPx ensure the achievement of the structural maturation of sperm cells as well as their protection against ROS-induced damage. We review here the roles played by the sperm-associated forms of GPx4 (mitochondrial GPx4 and nuclear GPx4), the secreted GPx5 protein, and the epithelial proteins GPx1, GPx3, and cellular GPx4, all functioning in the mammalian epididymis at different stages of the sperm's epididymal journey, and in different epididymis compartments.Journal of Andrology 03/2011; 32(6):641-50. · 2.97 Impact Factor -
Article: Dietary cholesterol-induced post-testicular infertility.
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ABSTRACT: This work shows that an overload of dietary cholesterol causes complete infertility in dyslipidemic male mice (the Liver X Receptor-deficient mouse model). Infertility resulted from post-testicular defects affecting the fertilizing potential of spermatozoa. Spermatozoa of cholesterol-fed lxr-/- animals were found to be dramatically less viable and motile, and highly susceptible to undergo a premature acrosome reaction. We also provide evidence, that this lipid-induced infertility is associated with the accelerated appearance of a highly regionalized epididymal phenotype in segments 1 and 2 of the caput epididymidis that was otherwise only observed in aged LXR-deficient males. The epididymal epithelial phenotype is characterized by peritubular accumulation of cholesteryl ester lipid droplets in smooth muscle cells lining the epididymal duct, leading to their transdifferentiation into foam cells that eventually migrate through the duct wall, a situation that resembles the inflammatory atherosclerotic process. These findings establish the high level of susceptibility of epididymal sperm maturation to dietary cholesterol overload and could partly explain reproductive failures encountered by young dyslipidemic men as well as ageing males wishing to reproduce.PLoS ONE 01/2011; 6(11):e26966. · 4.09 Impact Factor
