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Les gènes de la spermatogènese et leur régulation

Gene expression during spermatogenesis and their regulation

Résumé

La production de spermatozoïdes résulte d’un processus complexe et coordonné de division et de différenciation cellulaires appelé spermatogenèse. Chacune des étapes de ce processus, mitose, méiose et spermiogenèse est sous le contrôle de gènes exprimés de manière différentielle dans le testicule.

Le système c-kit/SCF régule la prolifération des spermatogonies tandis que l’équilibre entre l’expression des gènes pro- et anti-apoptotiques permet d’en limiter le nombre.

La méiose est sous le contrôle de plusieurs familles de gènes: 1) les gènes de protéines structurales nucléaires [lamines, histones, protéines du complexe synaptonémal]; 2) les gènes codant pour les enzymes du métabolisme énergétique [PGK, HK, PGAM …]; 3) les gènes codant pour les protéines de réparation de l’ADN et de la recombinaison méiotique; 4) les gènes du cycle cellulaire (gènes suppresseurs de tumeur, gènes du complexe cycline/CDC2, protéine HSP 70-2); 5) les gènes c-kit/SCF.

Enfin, le remodelage chromatinien survenant durant la spermiogenèse et reflétant la transformation d’un noyau actif sur le plan transcriptionnel en noyau spermatique quiescent, nécessite une expression séquentielle contrôlée des protéines basiques de liaison à l’AND: dans les spermatides les protéines histones et non histones sont remplacées par les protéines de transition qui à leur tour sont remplacées par les protamines dans les spermatides en voie d’allongement.

Parmi les gènes exprimés au cours de la spermatogenèse, on distingue: les gènes exprimés exclusivement au cours de la spermatogenèse;

les gènes codant pour une isoenzyme ou un isotype spécifiquement testiculaire de protéines s’exprimant dans les cellules somatiques (enzymes du métabolisme énergétique)

Les gènes exprimés au cours de la spermatogenèse, spécifiques ou non, subissent une régulation transcriptionnelle et/ou traductionnelle.

La régulation transcriptionnelle des gènes est essentiellement assurée par des facteurs de transcription qui peuvent être spécifiques des cellules germinales ou généraux mais exprimés de manière differentielle dans les cellules germinales. Les gènes des facteurs de transcription sont eux-mêmes soumis à une régulation particulière. Certains gènes exprimés dans le testicule résultent de l’utilisation d’un promoteur alternatif.

La régulation post-transcriptionnelle peutêtre assurée par un épissage alternatif des ARN ou l’arrêt au niveau d’un site de polyadénylation variable.

Des séquences régulatrices des régions 5′ et 3′ UTR contrôlent la traduction des gènes. La longuerr de la queue poly-A et certaines protéines se liant au niveau des régions 3′ et 5′ jouent un rôle majeur dans la régulation traductionnelle des gènes.

Abstract

Sperm production results from a coordinated and complex process of cell division and differenciation named spermatogenesis. Each stage of this process, spermatogonial division and differenciation, meiosis and spermiogenesis is under the control of a wide variety of genes, differentially expressed in the testis.

Spermatogonial multiplication is regulated by the c-kit/SCF system while the balance between pro- and anti-apoptotic genes expression allows the limitation of the number of these cells. Mammalian meiosis is regulated by many gene families. These include genes of: structural proteins of the nucleus (lamins, histones, synaptonemal complex components); enzymes of energy metabolism (pgk2, hk1-sa,-sb,-sc, pgam2, ldh3, pdha2, cyt ct and cs); proteins acting in DNA repair and meiotic recombination (rad 51, pms2, mlh1…); cell cycle (cyclin/CDC2 complex, tumor-suppressor proteins, HSP-70 protein); c-kit/SCF system. Spermiogenesis, the late stage of spermatogenesis is characterized by a dramatic remodelling of chromatin, which involves morphological changes and a highly regulated expression of the nuclear basic proteins: in round spermatids, both histones and non histone proteins are replaced by transition proteins and are eliminated from the cell. In elongating spermatids, transition proteins are removed from the condensing chromatin and are replaced by protamins.

Two categories of genes can be distinguished among those expressed during spermatogenesis: genes expressed exclusively in spermatogenic cells; genes expressed in somatic cells but coding for testis-specific iso-enzyme (enzymes of energy metabolism…)

In fact, the expression of genes during spermatogenesis is subject to transcriptional, post-transcriptional and translational regulation. The transcriptional control is mainly provided by transcription factors, which are neither specific of the germ cells or common but differentially expressed in germ cells. The genes coding for these transcription factors are themselves regulated. The choice of a specific promoter is another regulatory mechanism of some genes transcribed in the testis (CREM and CREB, cyt cs). The post-transcriptional regulation consits in an alternative splicing of some genes expressed in somatic cells (lamins C2, B3, HK1-sa,-sb, sc). Finally, translational regulation of genes expressed in male germ cells is particularly important during spermiogenesis. The length of the polyA tail and the presence of the 3′ and 5′ untranslated regions of the ARNm are importants elements in this regulation.

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Drouineaud, V., Jimenez, C. Les gènes de la spermatogènese et leur régulation. Androl. 10, 11–39 (2000). https://doi.org/10.1007/BF03035221

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