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David H. Volle,
Jean-Marie Frenoux,
Kevin Mouzat,
Patrick Vernet,
Magali Prod’Homme, Aurore Britan,
Fabrice Saez,
Joëlle Henry-Berger,
Ayhan Kocer,
Françoise Caira,
Georges Veyssiere,
Joël R. Drevet,
Jean-Marc A. Lobaccaro
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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.
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ABSTRACT: Using various molecular approaches, including reverse transcription-polymerase chain reaction (RT-PCR), rapid amplification of cDNA ends-PCR, sequencing, northern and western blotting, we found that the mouse GPX5 gene gives rise to at least three different transcripts that are not expressed at the same levels in the mouse epididymis. In addition to the major GPX5 transcript, we show that minor GPX5 transcripts exist, arising either from precocious termination of transcription or an alternative splicing event within intron 4 of the 5 exon-encoding GPX5 single copy gene. Furthermore, we demonstrate that variants of the GPX5 protein that are correlated with the shorter GPX5 transcripts can be detected in caput epididymidis protein extracts and that the various GPX5 isoforms are subject to differential post-transcriptional maturation processes in the mouse epididymis that essentially involve the addition of O-glycosyl extensions. Using a sensitive poly-A+ mRNA tissue blot, as well as RT-PCR and northern assays, we further show that in addition to being expressed in the epididymis, the GPX5 gene is also expressed, albeit at lower levels, in other tissues of the male genital tract, including the testis and prostate. Finally, we present evidence suggesting that the GPX5 gene is expressed in a temporally regulated manner during mouse embryonic development.
Reproduction Fertility and Development 07/2008; 20(5):615-25. · 2.11 Impact Factor
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ABSTRACT: Previous reports have suggested that indoleamine 2,3-dioxygenase (IDO) activity is particularly important in mouse epididymis tissue. We show here, using reverse transcription/polymerase chain reaction assays, Northern assays, Western blotting experiments, and immunohistochemistry that IDO is indeed highly expressed in mouse epididymis, and that IDO mRNA distribution and protein location are precisely regionalized within the organ and within sub-territories of the proximal part of the epididymal duct, the so-called caput epididymidis. Within the caput epididymidis, both the principal and the apical cells have been shown to express IDO. On the contrary, tryptophan dioxygenase (TDO), a sister enzyme of IDO, is weakly and uniformly expressed in mouse epididymis and, in contrast to IDO, is also expressed in testis. In the epididymis, TDO protein expression has been found in a totally different cell type in the smooth muscle layer surrounding the epididymal tubules. Finally, IDO is not secreted into the epididymal lumen, whereas the testis-expressed TDO is present on the head of spermatozoa retrieved from the cauda epididymidis. On the basis of the various functions that have been associated with IDO/TDO, we discuss the putative impacts of IDO/TDO expression on the physiology of mammalian epididymis and spermatozoa.
Cell and Tissue Research 06/2006; 324(2):301-10. · 3.11 Impact Factor
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Andrologie 01/2006; 16(3):197-228.
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ABSTRACT: It is well documented that a dietary deficiency in magnesium can induce oxidative stress and an inflammatory response in animal models. In our study, we have investigated these responses in the mouse epididymis after mice had been fed a magnesium-deficient diet for a 2-week duration. The extracellular and intracellular concentrations of magnesium where shown to be depleted on this diet. This was followed, however, only in the liver of the Mg-deficient animals, by an increase in both alpha 2-macroglobulin (alpha-2m), an acute phase marker, and interleukin-6 transcripts suggesting that an inflammatory response had been initiated. These changes were correlated with a decrease in circulating neutrophils. To address the question of whether or not peroxidation was induced in mouse epididymis following hypomagnesia, we have monitored the level of endogenous peroxidation, their ability to respond to induced peroxidation as well as the expression and activity of the enzymatic glutathione peroxidase (GPX) antioxidant family. To evaluate if the epididymis had evolved specific protections against peroxidation, other organs such as the liver and the kidney were monitored in parallel. We detected no evidence for increased peroxidation in any of the mouse organs tested. However, GPX activity was found to be significantly lower in the liver and the kidney of Mg-deficient animals while it was unchanged in the epididymides of the same animals during the deficiency. Histological analysis of the epididymis showed no major difference in the overall cytological aspect of the organ. Segment 2 of the caput, however presented a significant increase in the number of apically located cells or blebbing cells. Immunohistochemical analysis proved that these cells were epididymal apical cells and not infiltrated leukocytes. These observations suggested that the mouse caput epididymidis segment 2 specifically responded to Mg deficiency via the apical cells. Finally, a comparative analysis of stress response genes was conducted in control and magnesium-deficient caput epididymidis samples. It brought forward some genes that might be involved in the peculiar response of the caput epithelium following hypomagnesia.
Biochimica et Biophysica Acta 11/2004; 1675(1-3):32-45. · 4.66 Impact Factor
